ON CLIMATE CHANGE AND HEALTH

Health, good health of course, is the necessary and imperceptibly prior condition for our stability and our physical and emotional well-being. Our quality of life, and that of our loved ones, relates in many ways to the degree of strength of our health. That´s the reason why we fight all the endogenous and exogenous actions that disturb it or that deteriorate its normal healthy and balanced state. The quality of air, water, food, sanitation services and health care at different territorial and outpatient levels, allows us to measure the general physical health around us and the healthy or perverse effects of these matters over people and the social community where their lives unfold. The fight against climate change integrates many elements of health defense and protection, as well as against diseases associated with the lack of care for the natural environment. Doctor Loembé is an experienced and well recognized Medical Doctor and Scientist, graduated from the “Free University Medical Center” in Amsterdam, with more than eighteen years of experience in clinical oncology and cancer drugs research and development, and a growing interest in the impact that climate change has on the incidence and prevention of cancer. All this work, research and experience, will be reflected, and be part, of a book of imminent publication.

As a true and firm believer of science but also of equal opportunities for all – all men are created equal-, I admire Abraham Lincoln, son of a farmer and carpenter and unanimously considered as one of the greatest presidents of the United States of America. Thanks to his courage and, convinced that a divided house could not stand, he saved the Union.

Doris Kearns Goodwin masterfully describes Abraham Lincoln’s political talents and strengths in her Pulitzer Prize-winning book “Team of Rivals” where she brilliantly wrote how Lincoln, unexpectedly and against all odds, won the presidential election in 1860 above three accomplished candidates.

Unfortunately, five days after Confederate General Robert E. Lee surrendered his massive army at Appomattox Court House, Virginia, officially ending the American Civil War, on the evening of April 14, 1865, John Wilkes Booth, a famous actor and Confederate sympathizer, assassinated President Abraham Lincoln at Ford’s Theatre in Washington, D.C.

When I lately get to know more about Lincoln’s life and legacy, among all other statements and quotes, there is one that I considered as the most inspiring and which has guided me along my professional and personal life. In the conclusion on his first political announcement on March 9, 1832, Abraham Lincoln, while seeking his first seat in the Illinois General Assembly, mentioned:

“Every man is said to have his peculiar ambition. Whether it be true or not, I can say for one that I have no other so great as that of being truly esteemed of my fellow men, by rendering myself worthy of their esteem. How far I shall succeed in gratifying this ambition, is yet to be developed.”

I have decided to render myself worthy by modestly attempting to raise awareness on the impact of climate change on health. I hope that by the end of this chapter, I will unpresumptuously succeed to convince you and myself to take preventive actions to reduce the impact of climate change on health and particularly on cancer- a fourthousand-year-old disease-, which is one of the leading causes of death worldwide.

I am attempted to think and probably to admit that the crisis, if we can talk about crisis, about the global warming is not (yet) desperate, as “despair serves no purpose when reality still offer hopes”, had taught us Al Gore in Our Choice [ 1]. Undoubtedly there is hope, there are always been hopes and hopes had always given our humanity a hand when we had to face difficulties. Is not the young preacher from Georgia who was dreaming that one day, “We will hew up from a mountain of despair a stone of hope” in that sweltering August in 1963 in Washington DC? Is not the former legendary prisoner of Robben Island, who exhorted us that “there were many dark moments when my faith in humanity was sorely tested, but I would not and could not give myself up to despair. “Our faith is humanity is commonly tested now, I believe.

What should we do? Isn’t the young senator from Illinois, who after a victory for the democrats nomination for 2008 presidential election, addressing to supporters after the Iowa Caucuses, on Jan 3, 2008, discoursed “that hope is not a blind optimism, hope is that thing inside us that insists, despite all the evidence to the contrary, that something better awaits us so long as we have the courage to reach for it, to work for it , to fight for it.”

After we all, willingly and unwillingly, have acknowledged that our climate is dramatically changing, my hope is that we all together courageously and undauntedly will work together to raise awareness about the impact of climate change on health; that we all together unflinchingly and lionheartedly will fight for solutions to reduce the impact of global warming and health; that we all together consciously and audaciously will reach for a better clean world.

The United States of America has an impressive number of Nobel Prize winners. In the 104 years of its existence, the Nobel Prize has been awarded to close to 1,000 laureates and The United States is the highest Nobel Prize winning country, with 368 winners. The number of science publication in China has increased and overtaken the United States, nevertheless the Unites States remains a scientific giant producing out high profile research and translating science into valuable intellectual property [ 2]. Nonetheless, the United States has long been the world’s second largest consumer of coal. After a sustainable huge incline in consumption has been observed, the US dropped to the 3rd place behind China and India and is, as result, leading the world in reducing carbon dioxide emissions. In 2015, US carbon dioxide emissions was reduced by 145 million tons, by far the largest decline of any country in the world. This effort is not a scornful derision and should, in contrary, be commended. For the most recent 120 years, it comes forth that US emissions declined by 622 million ton which clearly represents a 10% decline over 10 years. This could be explained by power companies switching steadily from coal to natural gas. Despite this decline, overall the US is still the world second largest emitter of carbon dioxide. In 2015 the US emitted 5.5 billion tons of carbon dioxide representing 16% of the global total behind China (9.2 billion ton and 27% of the total global emission. [3]

There have been significant gains in life expectancy during the past half-century combined with declining fertility rates. It is forecasted that global life expectancy to increase by 4·4 years for men and for women by 2040. In 2040, Japan, Singapore, Spain, and Switzerland have a forecasted life expectancy that will exceed 85 years for both sexes, and 59 countries including China were projected to surpass a life expectancy of 80 years by 2040. At the same time, Central African Republic, Lesotho, Somalia, and Zimbabwe had projected life expectancies below 65 years in 2040 [ 4].

The profile of major causes of disease and death is being transformed; the pattern of infectious diseases has become much more understood and clinically manageable, though health inequalities between rich and poor countries unfortunately persist. There have been more drugs discovered, revolutionizing ipso facto the treatment of life-threatening diseases. The world has become an immensely close neighborhood where we eas

ily interact with each other. Nonetheless, today the prospects for future health depend to an increasing extent, on the processes of globalization and on the emergence of global environmental changes and challenges occurring in response to the great weight of man’s socio- economic activities. We are at a substantial crossroads where our daily actions have a significant impact on the living together tomorrow; which implies to ascertain that tomorrow is, veritably, today.

There are numerous of diseases which affect public health, and which could be directly or indirectly related to climate change. Among these diseases, we could, without blinking an eye, name cancer. We all know someone with cancer; we all have lost someone or a beloved because of cancer. How often didn’t we ask ourselves whether the cancer was not related to this food, to this place or to this habit? You would hear all unimaginable possible and impassable reasons that could be linked to cancer. The causes of cancer are multiple and various, well established and disputable and controversial at the same time. Among the well-established are genetic-hereditary predisposition, as well as environmental-life style-tobacco, human papilloma virus1 exposure, sun exposure. Environmental implies that these causes are undeviatingly, preventable. According to Cancer Research UK, 4 in 10 cancer can be prevented. Prevention measures include not smoking,

keeping a healthy bodyweight, eating healthy and balanced, cutting back on alcohol consumption, enjoying the sun safely and keeping active. These evidences and the related preventive actions are not clearly understood and not widely shared. This holds true for climate change and cancer. What are the straight irrevocable evidences currently known and what are the unswervingly corrective and preventive measures implemented so far?

Before answering these question, it is of significant importance to acknowledge that, as off today, there is a certain degree of skepticism in our society when it comes to climate change and diseases. For instance, what do we know about the babies born without arms in rural France? A mystery. The national health agency has launched a nationwide investigation and we are impatiently waiting for the outcome [ 109].

Yes, it takes time and tremendous effort to accept or establish the carcinogenicity of an agent. Let’s remember the story of tobacco. Before tobacco was accepted as carcinogenic, many years as well as many lives regretfully were lost.

Are there any similarities between smoking and climate change?

Doctor James Lee Gilmore (1884 -1863), a prominent smoker for years, was a 49 years old obstetrician gynecologist from Pittsburgh in Pennsylvania, who was admitted on February 27, 1933, to the medical and surgical chest service of Barnes hospital in St Louis, Missouri. Before this admission Dr Gilmore had been hospitalized repeatedly four times owed to pulmonary complains.

Since January 1929, Dr Gilmore had been diagnosed with pneumonia of the right lower lobe of the lung which recovered only several weeks later. Six months later, on July 1932, he experienced general discomfort, chills, fever and elevated white blood cell count. A chest radiography performed one month later revealed a shadow in the upper lobe of his left lung which (there is no record of an administrated treatment) regressed over the next days and recurred in October. After a slight remission, it recurred in December as an abscess leading to de novo pneumonia.

On February 27, 1933, he was admitted again with fever, chest discomfort that was suspicious for lung abscess. A performed X-ray showed a collapse of upper lobe of his lung. He underwent a bronchoscopy followed by a biopsy which revealed a presence of carcinoma-malignant tumor - made up of epithelial cells2. A follow-up bronchoscopy revealed a worsening of the tumor; a new biopsy was taken, which confirmed a squamous cell carcinoma of the left upper lobe. Dr Gilmore went home taking the biopsy slides with him for review, he got his dental cavities filled and purchased a cemetery plot.

On April 4, he was newly admitted in the Barnes hospital, in preparation for a left upper lobectomy3 by Dr Evarts Graham.

The surgery started at 10.00, precisely 25 minutes after anesthesia begun. After incision and opening the thoracic cavity, Dr Graham found multiple nodules obstructing the bronchi* which made a lobectomy unnecessary. Then, against all expectation, he decided to perform a pneumonectomy after discussion with Dr. Gilmore’s friend and brother-inlaw. Historically, a pneumectomy has never been performed in humans, but successfully in animals and obviously not by Dr Graham himself.

The day after having undergone the first pneumectomy in human’s history, Dr. Gilmore condition was satisfactory. He had had 8 hours without opiate but about 800 cc fluid had drained from the chest catheter. He was later taken again to the operating room to remove a portion of the second rib. Initially ribs 5-6-7-8 to 11 were already removed. On June 18, 10 weeks after the surgery, Dr Gilmore was discharged to go home. Dr Graham realized that he has for the first time performed a surgical procedure which will have significance consequences in the treatment of lung cancer. (C Barber Mueller, The life, lives and times of the surgical spirit of St Louis , chapter 7).

Dr Graham, considered by his last resident C. Barber Mueller as one of the three most eminent American surgeons, himself, was a tenacious smoker for more than 50 years, quitted, 5 years before he was diagnosed with bilateral bronchogenic carcinoma* in 1956. In 1920 Evarts Graham has ironized when he was asked for the first time whether tobacco caused lung cancer: ”so is the use of nylon stockings.”

Dr Graham was one of those who thought that “Blaming cigarettes for lung cancer was like blaming umbrellas for bringing on the rain. [5]

Three years before his death, Graham wrote in 1954 an essay in a book entitled “Smoking and Cancer”. He wondered how to fight the spread of tobacco in our society in the future, Medicine was not powerful enough, data were not enough, the solution is political and should come from the policymakers and from all of us, from each of us in our daily live. While his condition was deteriorating progressively, on February 14, 1957 he would write to his dear friend and colleague Alton Ochsner- who was not aware of his condition-, later that: “By the way my cancer is a squamous cell cancer apparently like all the other smoker’s lung cancers. I don’t think anyone can bring up a very forcible argument against the idea of a causal connection with smoking because after all I had smoked for about 50 years before stopping [ 6].

Some authors suggested a link between cigarette smoking and the increasing cases of lung cancer already in the 1920s and 1930s, but these reports did not have a tangible effect on consumption [ 7].

The battle to officially recognized tobacco as carcinogenic started in early 1940, when the Oxford epidemiologist Richard Peto wondered whether there could be a correlation.

Major epidemiological studies published in 1950 by Doll and Hill [8] and Wynder and Graham [9] definitively established that cigarette smoking causes lung cancer; additional confirmatory studies followed later and coming from the UK. In the winter of 1947 government statisticians in Great Britain, Doll and Hill, noticed that lung cancer morbidity was exponentially increasing nearly fifteenfold in prior two decades (Siddhartha Mukherjee, The Emperor of all maladies, Scribner 2010).

The higher mortality rate was observed in urban towns where the cigarette consumption was much higher and perceived as cool.

In the US, Ernst Wynder, a medical student on a surgical rotation was a witness of an unforgettable case of a 42 years old patient who had died from lung cancer whose autopsy revealed a typical smokers’ lungs. Wynder recruited a powerful mentor- Evarts Graham-, to research the connection between smoking and lung cancer. They both set up a trial including patients with lung cancer and a control group of patients without lung cancer. All patients were asked about their smoking history. This case control study demonstrated that, in the lung cancer group, smoking history was prominent. Nevertheless, when Wynder presented the data at a conference on lung biology in Memphis, the audience was skeptical, and no questions were asked insinuating that the correlation was weak and the interest, minor.

In October 1951 Doll and Hill, based on early presented study from Oxford geneticist Edmund Ford, who prospectively demonstrated that populations undergo defined genetic changes overtime, which implies that the changes should be captured in the real world and in the real time, set up a new prospective trial. They prospectively collected data about smoking history and death causes from more than 60.000 doctors in a centralized

registry of all doctors in Great Britain. From October 1951 to March 1954, 789 deaths were reported, among them 36 were due to lung cancer. All smokers!

It was when the fraction of smokers in the adult American catapulted to 45% that Richard Doll and Bradford Hill published their study in 1956. Concurrently, advertising from tobacco industries was increasing as never; targeting all population and even doctors. “More doctors smoke Camels” would be said in a Camel commercial. Shockingly, at the annual conferences of the American Medical Association in the early 1950, cigarettes were distributed free of charged to participants.

It is only in 1962, nearly 15 years after Doll and Wynder studies, the American Cancer Society, the American Heart Association and the National Tuberculosis Association sent a join letter to President Kennedy requesting to create a commission to investigate the connection between smoking and health. Luther Terry, the surgeon general was assigned as head of the committee. He appointed 10 members to his committee. The committee comprised of 5 smokers and 5 nonsmokers. They visited dozens of labs, reviews ton of data, interviews, opinions. 6000 articles, 1200 journals were reviewed. More than 1.123.000 men and women were included in this meta-analysis.

Slowly but irrefutably evidence of the link between smoking and cancer emerged. A 387 pages report recognizing tobacco as cause of lung cancer was finally released on January 1964. It was now the task of the Federal Trade Commission to regulate the abundant tobacco advertisement. In 1965 a bill entitled the Federal Cigarette Labeling and advertising Act was issued [ 10].

In Great Britain, the Royal College of Physicians published in 1962 the first report confirming the correlation between tobacco and lung cancer and other diseases.[ 11]

A new arena of “bloody” battle between tobacco industry and antitobacco lobbyists was open. In this battle lawyers such as John Banzhaf had successfully played a significant role to minimize the advertisement time for cigarettes on television.

Awareness started steadily and noticeably to rise each year but remarkably, it is from 1994 that a cigarette consumption in the US begun to drop for 20 straight years. Lung cancer incidence as well is decreasing.

What are the data today about smoking and lung cancer? 5.5 percent of male former smokers and 2.6 percent of women former smokers; 15.9 percent of current male smokers; 9.5 percent for current women smokers and 24.4 percent for male “heavy smokers” defined as smoking more than five cigarettes per day; 18.5 percent for women “heavy smokers develop cancer [ 108].

It has been estimated that up to 20% of all cancer deaths worldwide could be prevented by the elimination of tobacco smoking [ 12]. It is generally known that overall mortality among both male and female smokers in the United States is about three times higher than that among similar people who never smoked. More than 480,000 deaths annually 278,544 deaths annually among 201,773 deaths annually among women in the US. [13]

So many years lost, so many lives could undeniably have been saved, if we already in the early 50’s had the courage to acknowledge the carcinogenic effect of tobacco. To help this awareness, the tobacco advertising could have been broadly banned earlier and none of us would have ever been willing to identify himself to the Marlboro man with his horse, who was acknowledgedly, the symbol of manhood.

The causal correlation between tobacco and lung cancer has made a long onerous and burdensome journey before being universally accepted, because of discombobulation of the facts and denial of the reality. There is no worst blind that the one that do not want to see. What about the climate change? Should the hazardous connection between climate change and health have to travel the same long perilous journey before being extensively accepted?

Is it too late? Do we have a choice? Who is to blame? Passivity is a choice as such as action. What are the options? After all, what are the evidences available for the cynics among us? Is it appurtenant to question whether there is a causal correlation between climate change and health- cancer-? The cynics among us, for a fact, would remember William Edwards Deming and answer: “In God we trust. All others must bring data”.

Climate Change is happening

There are astounding amounts of data that demonstrates manifestly that the climate is changing. For several decades, the Intergovernmental Panel on Climate Change- the IPCChas been documenting the worldwide research that shows conclusively that the planet is warming from the gases we are releasing ( 14). Therefore, the intention, rather the objective is to put forward as much evidences as possible to help the acceptance of climate change as having a significant impact on health. In the hope that many lives could be saved before it

is too late, as it was too late as with tobacco. Climate change amounts to the global shift in weather patterns occurring over long periods. These changes could be -but not only- related to temperature, rainfall, winds speeds cloud cover and ozone depletion.

Climate change affects health directly by having an effect on clean air, safe drinking water, sufficient food and last but not least ozone depletion. It is expected that between 2030 and 2050, climate change would cause approximately 250.000 additional deaths per year, from malnutrition, malaria, diarrhea and heat weaves. The direct damage cost could raise up to USD 2-4 billion per year by 2030.

In order to assess the impact of climate change on health, it is worthwhile to elaborate explicitly on this impact with well-founded evidences, by analyzing which changes have an effect on health. Consequently, it is judicious to come up with recommendations for us as individuals, policymakers, politicians, researchers, business leaders and key opinions leaders.

Climate change has a very broad and diverse understanding and it is, appropriately, not an easy task to clearly and undeniably define the major drivers of it and their consequences, among which the impact on health. It is commendable as a matter of facts, to focus on few specific areas, which in my view require more attention considering the related burden.

Al Gore gained reign, as a climate defender, after the inconvenient truth witch made him a worldwide advocate of climate change. His voice was heard worldwide and the inconvenient truth has helped to increase awareness of the consequences of climate change.

After the success of An Inconvenient Truth, and our Choice, in “the Future”, he masterfully highlighted the six drivers of climate change.

• The emergence of deeply interconnected global economy

• The emergence of planet-wide electronic communication grid

• The emergence of completely new balance of political, economic and military power in the world

• The emergence of rapidly unsustainable growth- in population, cities; resource consumption; depletion of topsoil, freshwater supplies and living species; pollution flows

• The emergence of a revolutionary new set of powerful biological, biochemical, genetic and materials science technologies.

• The emergence of a radically new relationship between the aggregate power off human civilization and the earth ecological systems.

It is the question now which of these drivers impact our health? And how to align to find a common ground to mitigate the effect of these drivers?

The effect of climate change is variably immense, differently perceived and lived, but all aspects of the public health are concerned. According to the report from The In

teragency Working Group on Climate Change and Health published in April 2010, global climate change could increase the incidence of Asthma, Respiratory Allergies, and Airway diseases; Cancer, Cardiovascular disease and Stroke, Foodborne diseases and Nutrition, Heat-Related Morbidity and Mortality, Human Developmental Effects, Mental Health and Stress-Related Disorders, Neurological Diseases and Disorders, Vector borne and Zoonotic Diseases, Waterborne Diseases.

Causes of deaths worldwide

In 2016, 56.9 million deaths worldwide were reported; among them 54% were caused by the 10 most fatal diseases. Ischemic heart disease and stroke are the world’s leading cause of death, accounting for a combined 15.2 million deaths in 2016.

Chronic obstructive pulmonary disease claimed 3.0 million lives in 2016, whereas lung cancer (along with trachea and bronchus cancers) caused 1.7 million deaths. Diabetes killed 1.6 million people in 2016, up from less than 1 million in 2000. Deaths due to dementias more than doubled between 2000 and 2016, making it the 5th leading cause of global deaths in 2016 compared to 14th in 2000.

Lower respiratory infections remained the deadliest communicable disease, causing 3.0 million deaths worldwide in 2016 [ 15].

Projected global deaths in 2030 ranged from 64.9 million under the optimistic scenario to 80.7 million under the pessimistic scenario, with a baseline projection of 73.2 million [ 16].

Based on the aforementioned data from WHO, it is questionable what has been the contribution of global climate change on these painstakingly figures. Though there are no straight data from the WHO, but we could anticipate that the contribution of climate change is significant based on the mortality data from the studied environmental related deaths.

It goes without saying that, to cover all climate changes related diseases, an entire book will be needed instead of a chapter in a book. Therefore, it appears more appropriate to concentrate on the disease which cause the one highest mortality in the world: cancer

Since 1998, the American Centers for Disease Control and Prevention, The National Cancer Institute and the North American Association of Cancer registries have been collaborating annually to generate data on cancer incidence and mortality. In the report compiling data from 2010-2014, incidence and mortality of specific cancer sites such as female breast, Colo-rectal, lung and melanoma skin cancer declining. Cancer incidence is declining for 7 of the most 17 most common cancers among women and the incidence is increasing for 8 cancer sites among men and 10 sites among women. The most significant increase is observed for liver cancer, myeloma, melanoma of the skin, thyroid cancer and leukemia. The constant and continue increase in melanoma rate is associated with the increase of sun exposure and tanning bed use [ 17].

About 1.7 million new cancer cases were expected to be diagnosed in 2018 in the United Sates; and about 609,640 Americans were expected to die of cancer which is dramatically equal to about 1,670 deaths per day. Cancer is the second most common cause of death in the United States of America after heart disease. The Agency for Healthcare Research and Quality estimates that the direct medical costs (total of all health care costs) for cancer in the US in 2015 were $80.2 billion. Fifty-two percent of

those costs were for hospital outpatient or office-based provider visits, and 38% were for inpatient hospital stays [ 18].

Cancer biography and epidemiology

It is commonly thought and wongly perceived in our society that cancer is a modern disease. Although, chronological assessment of the incidence and occurrence of cancer in early fossil animal and human remains showed the scarcity of malignancies in antiquity, cancer is an old disease. Palaepathological findings from Egypt and Greece provide evidences about the possible diagnosis and treatment of cancer in the antiquity [ 111].

The first case of cancer was narrated by Imhotep, one of world history’s geniuses Inventor of the pyramid, author of ancient wisdom, architect, high priest, and essentially, a physician and astronomer who lived around 2625 BC. He described a female patient with a bulging mass, large, hard, cold to the touch, dense as a hemat fruit and spreading. For this case, Imhotep wrote that there is no therapy available. Based on this description, it could reasonably be assumed that it was a case of breast cancer.

Around 440 BC, 2 millennia after the case described by Imhotep, the story of Atossa, queen of Persia told by the Greek historian Herodotus, emerged and was as intriguing as it could describe Atossa suffering believably from breast cancer. She has a bleeding lump in the breast which was “to not avail”.

Presumably it was in the time of Hippocrates around 400 BC that a world cancer appears for the first time in the medical literature as karkinos from the Greek word for crab. According to Hippocrates the tumor, like the crab and his legs spread in a circle, will invade through the vessel with his legs [ 19]. Let’s remember Yefrem in Cancer ward from Solzhenitsyn mocking shamelessly to Pavel Nikolayevich, who was just admitted in the Cancer Ward of this filthy soviet hospital: “the crab loves people. Once he’s grabbed you with his pincers, he won’t let go till you croak” [110, page 19].

Cancer has inspired authors such as Alexander Solzhenitsyn to forcefully and forthrightly denounce the atrocities of the Stalinism in 1955, 2 years after the Stalinin’s death. In Cancer ward (110), Solzhenitsyn painted a picture of a deadly disease in relation to political repressive doctrine and love. He described the essence and nature of cancer in his most tragic forms, including it’s physical ,mental and social burdens; most importantly the particular relationship between cancer patients and the hospital caregivers.

Cancer is a disease which requires from the patients to go beyond human limits during treatment which, though beneficial in terms of survival, but could also be impacting severely the quality of life. Chemotherapy* is still the backbone of cancer therapy. The first chemotherapeutic agent was discovered by Sydney Farber, a pathologist born in Buffalo, New York in 1903, who, on September 6, 1947 successfully treated a two year old child-lethargic Robert Sandler with Leukemia, with Pteroylaspartic acid PAA, considered to be an antifolate*.[ 19, page 33]

Cancer is one of most widespread disease in the world and of the leading causes of death worldwide. The total number of new cases in 2018 was 18.078 million causing 9.6 million deaths in 2018. The most common cancers are:

• Lung (2.09 million cases, 11.6%)

• Breast (2.09 million cases, 11.6%)

• Colorectal (1.85 million cases, 10.2%)

• Prostate (1.28 million cases 7,1%)

• Skin cancer (non-melanoma) (1.04 million cases) • Stomach (1.03 million cases)

• Other cancers ( 7.75 million cases)

The most common causes of cancer death are cancers of:

• Lung (1.76 million deaths, 18,4%)

• Colorectal (880792 deaths, 9.2%)

• Stomach (782685 deaths, 8.2%)

• Liver (781631 deaths, 8.2%)

• Breast (626679 deaths, 6.6%)

• Oesophagus (508585 deaths, 5.3%)

• Other cancers ( 3,42 million deaths, 35.8%) *(20)

It is obvious that cancer is well established as a deadly disease with disastrous consequences for families. The mortality due to cancer is decreasing for some cancer types and at the same time increasing for others. It is our pertinacious tasks to identify the contribution of climate change in the increase of the incidence and mortality of certain types of cancers.

How is climate change contributing to cancer incidence and consequently to cancer related mortality?

Cancer is a group of disease, which affects different organs. It occurs when normal cells initially undergo a transformation and start growing uncontrollably, forming a mass called a tumor. Tumors are called cancer only if they are malignant. This means that they invade neighboring tissues (especially lymph nodes) because of their uncontrolled growth. Malignant tumors may also spread to distant organs via the bloodstream. This process of invading and spreading to other organs is called metastasis.

According to the European Climate adaption Platform, it is expected that by 20502080 the local climate In Cornwal, South West England will increase up to 3 degrees warmer, leading longer period of hot and dry weather. The increase in temperatures will lead to increase exposure to ultra violet radiation and consequently to increase incidence of skin cancer.

It is commonly accepted in our society that too much sun is disagreeable for our skin, How does it stand with the link between climate change, UV radiation- sun exposure, and skin cancer?

The case of Zacki Murphy

From cover girl to skin cancer patient, Model Zacki Murphy shares her story in skin cancer foundation delineating her personal experience at the time when she was on the spotlights as a model in “the Pursuit of False Perfection “.

A native of Hillsborough, North Carolina and a graduate of the University of North Carolina, Zacki Murphy was a popular model in 1970’s. Her face, hair and body were her paycheck, for this reason her skin had to look impeccably good and spotless. She was constantly asked to get a little more color by tanning and being regularly exposed in the sun. In her teenagers’ years, she would spent significant time in the sun and smeared herself with iodine and baby oil to amplify the effect of the sun. She always had the darkest legs when later she became a cheerleader. As a model she had multiple and numberless sun exposure specially for Vogue campaign, for which the shootings were taking place in very sunny exotic locations.

“Getting tanned is like an obsession” she narrated; and decades later she started to pay the price of the extreme sun exposure with a spot on the nose, which was diagnosed as skin cancer in 2015. She wrote further that:

“Once you suffer sun damage and especially once you have had skin cancer, your odds of developing future skin cancer go way up. After 28 years as a professional model, I look back and think about the countless ads I did for beauty companies what the public did not know and see, was the sun damage. I now know that avoiding tanning and practicing sun protection are the best ways to avoid skin cancer. Over the years I worked with Avon, Cover Girl Shishedo, Cotu, Maybelline, Merle Norman, Revlon, Oil of Olay and many other companies.” Be aware that the sun is a wonderful and necessary part of our existence, but it is not our skin best friend. We used to associate being tan with being healthy, but now, with the sun’s ray more intense than ever, we know better.” [21]

Ultra violet radiation and skin cancer

At the beginning of last century, the upcoming industrial revolution, the migration of impoverished rural masses into urban centers, and the virtual chaining of the human work force to factories far from any ray of sunlight, paved the way for the desire to go outdoors and spend more time exposed to the sun. This, together with the discovery of the beneficial effects of sunlight for some conditions, eventually created increasing last century’s drive and obsession to the beaches. Being tanned started to be considered as a hallmark of beauty, fashion and social prestige in the West.

Many fashion houses and designers built on this by pushing the idea that, a suntan was beneficial and industriously attractive in terms of fashion. Only in the second half of last century did the rapid increase of biologic data help us to better understand skin biology, including photobiology. And only then a relation to phototypes was made, longitudinal and epidemiologic studies were initiated, to investigate the harmful effect of the sun; and a more differentiated perspective of the interaction between sun and skin was set in [ 22].

Ultraviolet Radiation exposure was first linked experimentally to skin cancer in the 1920s [23] In his publication Findlay, from the Laboratories of the Imperial Cancer Research Fund, London, noted that “It has long been known that prolonged exposure to the weather may produce, in the exposed skin, changes which not infrequently terminate in cancer.” These changes were first described in 1896 by Paul Gerson Unna, German dermatologist from Hamburg and one of the pioneers of dermatopathology, under the name “Seemanshaut,” or sailor’s skin; since the condition was especially common in sailors [ 24]. The American Hyde, in 1906 [25] and the French Dubreuil in 1907, published the first evidences linking human skin cancer to sunlight. [26]

There are three major types of skin cancers distinguished: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. The first two skin cancers are grouped together as non-melanoma skin cancers. SCC is more dangerous and is responsible for the most skin cancer related deaths. Overall, 80 % of skin cancers are BCC, 16 % are SCC and 4 % are melanoma. [27]

Generally fair skin, red and blond hair, blue or green eyes are more susceptible to skin cancer [ 28].

Exposure to Ultra Violet radiation is the main factor that causes skin cells to become cancer cells.

Almost all skin cancers -approximately 99% of non-melanoma skin cancers and 95% of melanoma-, are caused by excessive UV radiation from the sun or other sources such as solaria (solariums, sunbeds, and sun lamps).

What is Ultraviolet Radiation?

UV radiation is part of the electromagnetic (light) spectrum that reaches the earth from the sun, a 6 billion old star, and is invisible to the naked eye. These wavelengths are classified as UVA, UVB, or UVC, with UVA the longest of the three at 320-400 nanometers. UVA is further divided into two wave ranges, UVA I, which measures 340-400 nanometers (nm, or billionths of a meter), and UVA II which extends from 320-340 nanometers. UVB ranges from 290 to 320 nm. With even shorter rays, most UVC is absorbed by the ozone layer and does not reach the earth [ 29].

Both UVA and UVB, however, penetrate the atmosphere and play an important role in conditions such as premature skin aging, eye damage (including cataracts), and skin cancers. They also suppress the immune system-reducing your ability to fight off these and other maladies.

It is estimated that ultraviolet radiation constitutes only 7% of the solar energy that reaches the skin; 39% is in the visible light spectrum (400–760 nm). But 54% of solar energy consists of infrared radiation [ 30].

As defined earlier, there are two types of UV radiation. A and B; but the highest risk of skin cancer is related to UVB exposure by causing more genetic damage, whereby it contributes to about 80% sunburn, whereas UVA contributes to the remaining 20% [ 31]. It is obvious that UV radiation exposure is the leading cause of skin cancer. It is well established that the depletion of the one layer worsen the effect of the sun exposure on the skin.

Skin cancer develops in the cells in the epidermis – the outer layer of the skin. UV radiation is made up of two types of radiations: UVA and UVB rays which are both able to penetrate the skin and cause permanent damage to the skin cells.

UVA penetrates more deeply into the skin (the dermis) causing genetic damage to cells, such as wrinkling, blotchiness; and immune-suppression whereas UVB penetrates into the epidermis (top layer of the skin) causing damage to the cells.

Excessive UV radiation from the sun or sunbeds would eventually damage the genetic material (DNA) of the skin cells. In case significant DNA damage is built up over time, it can lead to an uncontrolled growth of cells leading to skin cancer.

Exposure to solar UV radiation depends on a number of factors, including latitude, elevation, the presence of reflective surfaces, ozone concentration, cloud cover, and particulate matter in the atmosphere [ 32].

Stratospheric Ozone

Although they received the Nobel prize together with Crutzen in chemistry only in 1995, for their work in atmospheric chemistry , Molina and Rowland, demonstrated already earlier that stratospheric ozone might be destroyed by industrially produced chlorine- and bromine-containing stable substances, such as chlorofluorocarbons* commonly used in spray cans, refrigerators and air conditioners. These inert substances can reach the stratosphere*, where they are decomposed by high-energy UV radiation; consequently, reactive chlorine and bromine are released [ 33].

Resultantly, the ozone depletion will reduce the damping effect of UV radiation even if the sun exposure will remain the same. It should be acknowledged that, normally, people need reasonable daily exposure to ordinary levels of UVB radiation to maintain their vitamin D levels and their adaptation to sun exposure, but overexposure will contribute to adverse effects such as immunosuppression and skin cancer [ 34]. Exposure to sun is one of the source of vitamin D which contribute to reduce the risk of breast cancer. Correspondingly, UV radiation causes damage on DNA leading to several mutations of genes; most importantly of the P53 which is considered as the guardian of human genome.

It has been demonstrated, in addition, that genetic alterations within the p53 gene* have a direct correlation with cancer development and occur in nearly 50% of all cancers. p53 mutations are particularly common in skin cancers caused by UV irradiation.[ 35]

As specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation, it has been suggested that measurement of these mutations may be useful as a biologically relevant measure of UV exposure in humans and as a possible predictor of risk for skin cancer [ 36].

According to a study from Van der Leun, based on mouse experiment, increased room temperature enhanced ultraviolet (UV) radiation-induced carcinogenesis; the effec

tive UV dose was increased by 3-7% per °C. Hence, the aim of the study was to research the effect of climate change on the incidence of skin cancer in the US, based on a survey in 11 regions. It was demonstrated that the increase of the incidence of non-melanoma skin cancer was related to the increase of temperature, thus of ambient UV radiation exposure. For squamous cell carcinoma, the incidence was higher by 5.5% per °C and for basal cell carcinoma by 2.9% per °C. These values correspond to an increase of the effective UV dose by about 2% per °C. The study concluded that the temperature rises associated with climate change could undoubtedly increase the induction of non-melanoma skin cancers by UV radiation in human populations. [37]

Therefore, there are international agreements on ozone-depleting substances, described in the Montreal Protocol of 1987 and its later amendments to reduce the depletion of the ozone layer [ 38].

The persistent degradation of the ozone layer will likely lead to a dramatic increase in skin cancer incidence, which is estimated to increase fourfold by the year 2100 [ 39].

The incidence of both Melanoma and Non Melanoma Skin Cancer is on the rise, with an annual increase in MM of 0.6% among adults over 50 years [ 40]. This is an unconventional and imperfect truth we have to face and to deal with. Daily!

The observed increases in skin cancer incidence could be associated, on one hand with the significant older populations [41] and on the other hand with the important role of increased occupational and recreational UV light exposure. [42]

For instance, women <40 years exhibited a constant linear increase in BCC incidence rates of 6.3% between 1973 and 2009 [ 43].

Others authors such as Lens et al have published extensively on the increase of the incidence of malignant melanoma , responsible for 1-2% of all cancers and 75% of all skin cancer deaths [ 44]. For instance, in Ireland from 1994-2012, the incidence of melanoma has increased annually by 3% and 5% in females and males, respectively. Mortality rates are also on the incline, with a 2.2% and 6% annual rise in melanoma related deaths in females and males, respectively [ 45]. From all these data, ultraviolet radiation has been incriminated as the important contributing factor, particularly intermittent exposition to sunlight [ 46].

Numerous studies with animal’s models had convincingly demonstrated that skin cancer is associated with a failure of the immune system to recognize tumor antigens and/ or to destroy malignant cells. In this context, UV-induced skin cancers may be viewed as the result of failed surveillance system by the immune system.

The scientific data abovementioned are, in my opinion, convincing enough that there is a fierce urgency that full compliance of all nations and industries with the international agreements will help to reduce the ozone depletion and to accelerate his recovery.

The individual responsibility is also required to help the nations and industries. We are all concerned, and inactivity could be fatal and contribute to increase the incidence of skin cancer.

International conferences on UV and skin cancer prevention

To raise awareness about the prevention of skin cancer, international experts in skin cancer prevention, UV radiation science, dermatology, allied behavioral and clinical disciplines and members of the environmental planning and design communities, gather for the international conferences on UV and skin cancer prevention. The 4th edition was held in North America in Toronto from 1st May to 4th May, after the successes of past conferences in Copenhagen (2011), Berlin (2013) and Melbourne (2015). Skin cancer is the most common cancer in North America.The objectives of the 4th conference was:

• Bring together the leading international researchers and practitioners in skin cancer prevention to showcase the latest research findings and best practices in community-based interventions

• Create collaborative opportunities between the skin cancer prevention community and allied disciplines such as urban planners, architects, and radiation scientists

• Respond to current concerns about gaps in the skin cancer prevention literature

• Foster discussions about innovative emerging directions in skin cancer prevention research and practice. [47]

Kristie L. Ebi, PhD, Jennifer Vanos respectively professor at Rohm & Haas Endowed Professor, Public Health Sciences and the University of Washington (USA), in the plenary session 2 presented a topic on “Environmental Issues in Skin Cancer Prevention Incorporating Climate Change in Skin Cancer Prevention Interventions”. They highlighted that “interactions among environmental, social, and economic factors could affect skin cancer prevalence, with the magnitude and pattern of changes varying spatially

and temporally. The main pathways are through changes in erythemal irradiance and through changes in human activities and behaviors that could increase or decrease UV exposures and the risk of skin cancer. “They advocated further to reduce greenhouse gas emissions to address the impact of climate change on the increasing erythemal irradiance. Earlier and warmer springs invite people to spend more time outdoors, engaging in leisure-time physical activity in clothing that could increase exposure to UVA and UVB if sunscreen use. In fine, increasing awareness of how climate change could alter the risks of skin cancers is needed among health care providers and the general public to ensure that preventive measures are timely and effective. Increased monitoring and research are needed to improve estimates of UVR exposure, to better quantify UV exposures, and to inform effective modifications of population-based interventions in the face of a changing climate to prevent an increase in skin cancers.

In her presentation entitled: “Alliance for UV Protection: Prevention of Health Damage Caused By The Sun - Structural Prevention in Urban and Rural Areas” Cornelia Baldermann from the German Federal Office for Radiation Protection in Neuherberg, Germany, also noticed that “The number of UV radiation induced skin cancer continues to rise in Germany as well as worldwide. The situation is further exacerbated by climate change. Climate change is also the cause for more high temperature days with increased morbidity and mortality “

What about forecasting the level of UV radiation? Yves Rochon from Environment and Climate Change Canada, Toronto, ON, and Jean de Grandpré from Environment and Climate Change Canada, Dorval, QC. emphasized that the development of a comprehensive Chemical Data Assimilation (CDA) system which can be used for various air quality applications and also UV index forecasting is being completed. The objectives will be:

1. Inform the community of progress at Environment and Climate Change Canada in UV index forecasting.

2. Provide insight as to how the UV index is determined from ozone and weather model forecasts with this new system.

3. Provide insight on the reliability of these new UV index forecasts

Depletion of stratospheric ozone by man-made gases such as chlorofluorocarbons has been occurring during the past few decades and is likely to peak by about 2020. Ambient ground-level ultraviolet irradiation is estimated to have increased by up to 10% at mid-to-high latitudes during the past two decades [ 48].

After 8000 generations of homo sapiens, our generation is witnessing the unavoidable process of human caused depletion of stratospheric ozone. Most of the ozone resides within the stratosphere and the ozone absorbs most of the solar UV radiation. Nevertheless atmospheric ozone is not originally part of the planet system but a product of life on earth . About 2 billion years ago as photosynthesizing organism emitted oxygen, a waste gas called ozone begun gradually to form within the atmosphere. The ozone layer depletion is caused by various industrial halogenated chemical such as chlorfluocarbons (CFC) used in the refrigeration and insulated packaging and spray cans propellants. (A.J Michael, R Lucas A.L Ponsonby, S J Edwards, Climate change and human health stratospheric ozone depletion ultraviolet radiation and health chapter 8.

As mentioned earlier, UVR exposure was first linked experimentally to skin cancer in the 1920s in mouse models (Findlay, G.M. Ultraviolet light and skin cancer. Lancet 2: 1070–1073 (1928). The association between stratospheric ozone depletion and skin cancer was first established in the 1970s. Subsequently the International Agency for Research on Cancer in 1992 concluded that solar radiation is a cause of skin cancer [ 49].

Mc Kenzie et al have demonstrated that sustainable decreases in summertime ozone over Lauder in New Zealand led to significant increases in peak ultraviolet (UV) radiation intensities. In the summer of 1998–99, the peak sun burning UV radiation was about 12 percent more than in the first years of the decade. [50]

We all remember the colour-enhanced pictures of the winter-spring polar “ozone hole” on the United States NASA web-site depict an overall loss which had keppt up to around one third of total Antarctic ozone, by the late 1990s, relative to the pre-1975 figure. Winter-spring losses in the Arctic are smaller because local stratospheric temperatures are less cold than in the Antarctic. During the 1980s and 1990s at northern mid-latitudes (such as Europe), the average year-round ozone concentration declined by around 4% per decade: over the southern regions of Australia, New Zealand, Argentina and South Africa, the figure has approximated 6–7%. Long-term decreases in summertime ozone over New Zealand are associated with significant increases in ground level UVR, particularly in the DNA-damaging waveband [ 51].

The Montreal protocol

Two years after the discovery of the Antarctic ozone hole in 1985, nations of the world signed the Montreal Protocol on Substances that Deplete the Ozone Layer, which regulated ozone-depleting compounds.

The Montreal Protocol finalized on 26 August 1987 -and which entered in forced 2 years later, is a global agreement to protect the stratospheric ozone layer by phasing out the production and consumption of ozone-depleting substances. It was a protocol to the Vienna for the protection the ozone layer.

The protocol has had in total eight revisions:

• in 1990 (London, Phase out of CFCs4 and other harmful Ozone depleting substances is set at 2000 for developed and 2010 for developing countries),

• 1991 (Nairobi, The Multilateral Fund is established to finance phaseout projects in developing countries),

• 1992 (Copenhagen, Phaseout of CFCs is accelerated to 1996 and hydrochlorofluorocarbons (HCFC) phaseout is targeted to begin in 2004 for developed countries),

• 1993 (Bangkok, Phaseout of HCFCs is accelerated for developed countries to start ten years earlier),

• 1995 (Vienna, Phaseout of methyl bromide is set to 2010 and HCFC phaseout is moved from 2030 to 2020 for developed countries),

• 1997 (Montreal, Phaseout of HCFCs is established for developing countries),

• 1998 (Australia, ozone protection amendment bill to make the regulation of the importation, manufacture and export of hydrochlorofluorocarbons (HCFCs) and methyl bromide more equitable, operable and effective),

• 1999 (Beijing, Controls on the production and trade of methyl bromide and HCFCs are tightened),

• 2016 (Kigali, Phasedown of HFCs is established).

Full implementation of the Montreal Protocol is expected to result in avoidance of more than 280 million cases of skin cancer, approximately 1.6 million skin cancer deaths, and more than 45 million cases of cataracts in the United States alone by the end of the century, with even greater benefits worldwide. The Montreal Protocol’s Scientific Assessment Panel estimates that with implementation of the Montreal Protocol we can expect near complete recovery of the ozone layer by the middle of the 21st century.

The Montreal Protocol has proven to be innovative and successful, and is the first treaty to achieve universal ratification by all countries in the world in the history of the

United Nations [ 52]. Former United Nations Secretary-General Kofi Annan remarked on the success of this global response by saying, “perhaps the single most successful international environmental agreement to date has been the Montreal Protocol.”

In November 2017, the EPA United States Environmental Protection Agency, issued a report on “Stratospheric Ozone Protection: 30 Years of Progress and Achievements”. According to this report, the United States is exceeding its Phaseout Obligations. The United States has implementing a range of domestic actions under Title VI that have led to meet and exceed the ODS phaseout outlined under the Montreal Protocol.

Technological Improvements Stimulated by the Montreal Protocol as mentioned in the 30 years report from the EPA on the Montreal protocol

1. Refrigeration and Air Conditioning Equipment Manufacturers. Manufacturers of refrigeration and air conditioning equipment re-designed their equipment to improve energy efficiency and reduce refrigerant leakage rates, which also resulted in reduced operating costs.

2. Aerosols Industry. This industry developed “not-in-kind” alternative delivery systems to ODS-propelled aerosol cans, such as spray pumps and roll-on deodorants, which are safe for human and environmental health and more cost-effective than aerosols.

3. Solvents Industry. To reduce the use of solvents to clean metal parts, deflux wiring assemblies, and remove contaminants from precision mechanical parts in the electronics industry, the solvent cleaning industry developed new solder fluxes and pastes that do not require cleaning or can be leaned with water.

4. Agricultural Fumigants. High-barrier tarps are now used in the agriculture industry in response to the phaseout of methyl bromide. These tarps are laid on top of a fumi-

gated field and significantly reduce atmospheric emissions and bystander exposure to fumigants while achieving effective pest control.

In 2015 in his report titled, “Updating ozone calculations and emissions profiles for use in the atmospheric and health effects framework model“, EPA modeled the effects of a depleted ozone layer on Americans born between 1890 and 2100, a timeframe that includes those who were very old when the ozone hole was discovered and those who will be very young when the ozone layer is fully recovered. The modeling showed that full implementation of the Montreal Protocol is expected to result in the avoidance of more than 280 million cases of skin cancer, approximately 1.6 million skin cancer deaths, in the United State [53] Updating Ozone Calculations and Emissions Profiles for Use in the Atmospheric and Health Effects Framework Mode ) resulting in hundreds of billions of dollars in societal health benefits in the United States over the period 1990 to 2165.

For the first time, scientists have shown through direct observations of the ozone hole by a satellite instrument, built by NASA’s Jet Propulsion Laboratory in Pasadena, California, that levels of ozone-destroying chlorine are declining, resulting in less ozone depletion.

Measurements show that the decline in chlorine, resulting from an international ban on chlorine-containing human-produce chemicals called chlorofluorocarbons (CFCs), is resulting in about 20 percent less ozone depletion during the Antarctic winter in 2005 - the first year that measurements of chlorine and ozone during the Antarctic winter were made by NASA’s Aura satellite [ 54].

Economics burden of skin cancer

Health has indisputably been related to high costs. Screening, diagnosis and treatment are the most important sources of spending. This particularly holds true for cancer. Non Melanoma Skin Cancer has a significant economic burden. In Australia, it is the most costly cancer, accounting for expenditure of AUS$511 million in 2010. Non Melanoma Skin Cancer treatments increased by 86% between 1997 and 2010. It was anticipated that the number and the total cost of NMSC treatments will increase by a further 22% between 2010 and 2015. NMSC will remain the most costly cancer and place an increasing burden on the Australian health care system ( 55).

In United Kingdom, it is estimated that costs due to skin cancer were in the range of £106–£112 million in 2008 and that the cost to the NHS due to skin cancer will amount to over £180 million in 2020 (56) .The costs of treatment and morbidity associated with Basal Cell Carcinomas place a heavy economic burden on public health and patients, their families and also on governments. We should all, including the policymakers, make more effort to underpin the importance of efficient management and prevention efforts directed toward this malignancy.

In the USA, it has been estimated that total annual NMSC-related expenditure is US$650 million, with Medicare costs 6–7 times greater than those for treating melanoma [ 57]. The analyses of a study by Ghent University in collaboration with the Foundation

against cancer, showed that the total economic burden of skin cancer in 2014 in Belgium, was estimated at €103.2 million. The majority of this total cost was due to Melanoma skin cancer representing 62% of the costs.

Conversely costs for the patient were higher in case of non‐melanoma skin cancer. It is estimated that both primary prevention programs (prevention campaign and ban on sunbed use), would be cost‐savings. The budget impact analysis revealed that for every euro invested in the prevention campaign, €5.7 would be saved on the long term (over 50 years). Both screening strategies resulted in a gain in QALYs* over a period of 20 years [ 58].

An estimated 2,846 (5.3%) of the 53,696 newly diagnosed cases of basal cell carcinoma (BCC) and 1,710 (9.2%) of the 18,549 newly diagnosed cases of squamous cell carcinoma (SCC) in 2011 in Canada, were attributable to occupational solar radiation exposure. The combined total for direct and indirect costs of occupational NMSC cases is $28.9 million ($15.9 million for BCC and $13.0 million for SCC), and for intangible costs is $5.7 million ($0.6 million for BCC and $5.1 million for SCC). On a per-case basis, the total costs are $5,670 for BCC and $10,555 for SCC [ 59].

1.5 million Canadian workers are exposed to solar UV at work, and approximately 900,000 of them spent more than 75% of their workdays outdoors (e.g., construction workers, farmers, and landscapers) and have a high level of exposure to solar UV ( 60).

The costs related to skin cancer are admittedly very high; the most western countries are facing budget deficit and are eager to cut on health costs. Rising awareness for prevention is less costly and should be worth our attention and effort. As it is “Better to prevent that to heal”, it should be crystal clear that preventing is cheaper that treating. We do not have another choice to act now as these costs could be allocated to found more

modern structures, to reform social and education systems. It is a mandate of conscience to have a new vision and to daringly answer this call which impacts our own daily lives and which, at the same time goes beyond our own boarders.

Lung cancer

According to The American Cancer Society, estimation for lung cancer in the United States for 2019 will be: about 228,150 new cases of lung cancer (116,440 in men and 111,710 in women) and about 142,670 deaths from lung cancer (76,650 in men and 66,020 in women). Worldwide it is estimated that there were 2 093 876 new cases of (accounting for 11.6% of all types cancer.

In 2018 the Globocan5 estimated 1.761007 deaths due to lung cancer and accounting for 18,4% of all cancer related deaths whereas for colorectal it was :880.792 (9.2%), 626.679 (6.6%) for breast and 358.989 (3.8%) for prostate.

Lung cancer is by far the leading cause of cancer death related among both men and women. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined.

The incidence rate has been declining since the mid-1980s in men, but only since the mid-2000s in women, because of gender differences in historical patterns of smoking uptake and cessation. From 2005 to 2014, lung cancer incidence rates decreased by 2.5% per year in men and 1.2% per year in women.

Lung cancer imposes a major disease burden on the world. Worldwide, lung cancer remains the most common cancer diagnosed and greatest cause of cancer-related death.

Lung cancer rates vary around the world, reflecting geographical differences in tobacco use and air quality.

Undoubtedly the incidence of lung cancer has been declining due to smoking cessation as result of intense and strong preventive policy worldwide. unfortunately, the number of cases related to environmental factors excluding tobacco are in the rise. More effort could be made to reduce the impact of other factors such as Radon and air pollution to reduce the incidence rate of lung cancer.

Climate change and lung cancer

Environmental risk factors of lung cancer

Though tobacco is considered as the leading cause of lung cancer (80%), the focus of lung cancer in nonsmokers is growing, taking into consideration that there are other multiple risk factors that are associated with lung cancer. Among these risk factors, there are radon -is the second leading cause of lung cancer-, and air pollution.

Residential radon from soil accounts for the second most common risk factor for lung cancer, accounting for approximately 10% of the cases [ 61].

Radon exposure

According to the Environmental Protection Agency, in the United States, Colorado is one of the States with high residential radon concentrations. Conversely the incidence of lung cancer was 54.7 versus 67,7 nationwide per 100.000. The annual death rate due to lung cancer in Colorado (41.8 per 100.000 in the 1998-2002 period) while the national death rate due to lung cancer was higher (55.7%). Are then the risks are mentioned by EPA speculative? [ 62].

Everyone is exposed to radon, but some populations as described in the literature, are at higher risk of exposure to increased radon levels than others leading to increase health risk. Approximately 6 million homes in the United States have radon levels above 4 picocuries per liter (pCi/L), which is the remediation level EPA recommends. ( * ATSDR, 2010). EPA estimates that at its recommended guideline of 4 pCi/L, the risk of developing lung cancer for a lifetime exposure to radon is

• 1% for nonsmokers,

• 3% for former smokers, and • 5% for smokers.

Chronic exposure to radon and his decay products is a well know and established second leading cause of lung cancer. We know that alpha particle emissions from inhaled radon

decay product cause lung cancer [63] causing molecular damage leading to DNA mutations and chromosomal strands breaks (Boris B.M. Melloni, European Respiratory journal 2014 44: 850-852) and the risk for lung cancer is significantly higher for smokers than for nonsmokers. More than 85% of radon-induced lung cancer deaths are among smokers.

What is Radon?

When you fight an invisible but known enemy, you have a chance to win a battle even the war, with the right army and strategy. The Chinese legend taught us in the Battle of Wuzhang Plains, that “A dead Zhuge scared away a living Zhongda “. When there is an unknown enemy, we seat in our comfort zone and position ignoring the danger that looms in the horizon. Because, understandably, we do not even know how to fight and whom to fight, even when we have the best army and strategy. So, knowledge and awareness are key. Knowing your enemy, if any, is cardinal and regnant.

Radon is a colorless, odorless, radioactive gas which is a breaking down product of radioactive elements, such as uranium, which a are found in different amounts in soil and rock worldwide Radon gas in the soil and rock can move into the air and into underground water and surface water.

There is a controversy as to who discovered radon. The discovery of Radon was allegedly, wrongly attributed to the German physicist Friedrich Ernst Dorn, (1848-1916), Professor from Friedrichs Universihit, Halle (Saale), whereas Ernest Ruthrhord (1871-1937), Professor of McGill University from Montreal, Canada seems to be the discoverer. Rutherford first characterized emanation of a radon isotope (from thorium) as a gas and an element and should be credited with the discovery of radon. Dorn was the first to observe emanation from radium specifically (the etymological source of the name “radon”), but his observations were subsequent to Rutherford’s work [ 64]. Two of radon’s isotopes* (radon-220 and radon-222) are progeny in two decay chains that begin with naturally occurring thorium and uranium, respectively, in rock, soil, water, and air. It is an inert gas of 86 with a mass of the most stable isotope of 222. It is chemically an inactive gas and is 7.6 times heavier than air and could readily be dissolved in water; slightly acidic and poor in mineral, alcohol and fatty acids. It emits alpha radiation [ 65].

Radon breaks down into solid radioactive elements called radon progeny* (such as polonium-218, polonium-214, and lead-214). Radon progeny can attach to dust and other particles and can be

breathed into the lungs. As radon and radon progeny in the air break down, they give off radiation that can damage the DNA inside the body’s cells. (Being exposed to radon for a long period of time can lead to lung cancer. Radon gas in the air breaks down into tiny radioactive elements (radon progeny) that can lodge in the lining of the lungs, where they can give off radiation. This radiation can damage lung cells and eventually lead to lung cancer [ 40].

Radon is present not only outdoors but also indoors. It is normally found at very low levels in outdoor air and in drinking water from rivers and lakes. It can be found at higher levels in the air in houses and other buildings, as well as in water from underground sources, such as well water. When inhaled into the lung, alpha particles emitted by shortlived decay products of radon can damage cellular DNA. Cellular mutagenesis studies, experimental research in animals, and occupational epidemiologic studies have established radon as a human lung carcinogen [ 66].

Concentration of radon are low outdoors but could be high indoors specially in home. Urban areas trends to have more lower radon concentrations than rural ones as the underlying rock is usually

The normal dose of radon in the US is established at 4 picocuries

Studies have showed that there is a synergistic effect between radon and tobacco smoke [ 67]. These studies were conducted in Europe among 150 people with lung cancer and 150 control group incorporated detailed smoking history and radon exposure.

The U.S. Environmental Protection Agency (US EPA) and the Surgeon General’s Office have estimated that as many as 20,000 lung cancer deaths are caused each year by radon. Radon is the second leading cause of lung cancer. Radon-induced lung cancer costs the United States over $2 billion dollars per year in both direct and indirect health care costs.

Radon is the leading environmental cause of mortality related to cancer. Radon induced lung mortality is seventh leading cause of cancer mortality in the US,

In 1986 Environmental and protection agency (EPA) and the department of health a and human services recommended radon screening for most homes in the USA. In 1992 the recommendation was amended requiring a double strategy for measuring residential radon. First short-term measurement followed by a confirmatory measurement if the screening measurement was 4 pCi/L or greater. The number of preventable lung cancer by the first screening is estimated to be 811 and by the second screening 527 [ 68]. But what has Radon to do with climate change? Again, know your enemy and define align the strategies.

Climate change is leading to longer spring and fall, and the summer are accompanied with hit waves which is indisputably having impact on indoor air exchange.

Climate change is undoubtedly affecting depositional environment within home that is impact in dose of radon decay product in homes [ 69]. The dose of Radon and his decays is impacted by the building ventilation rate.

To all appearances, exposure risk scenario to radon is changing as result of climate change. Currently buildings are better sealed to make them more energy efficient to mitigate the climate changes effects. The indoor concentration of radon is undeviatingly increasing with sealed building. Countries as US and UK have Radon mitigation design standards and buildings codes used for design and construction of buildings whereas some other countries which are heavily confronted with climate changes effects / New Zealand and Australia-, do not have [ 70].

The increased use of ceiling fans for cooling could impact the dose of radon decay products leading to a reduce dose of radon to the lung [ 71].

Contrarily, the use of air conditioning may reduce the use of ceiling fans and therefore enhance the delivered dose by radon progeny.

The direct measurement of the dose rates produced by radon progeny in air is hardly possible in radon atmospheres with high activity concentrations, because the major contribution of measured dose rates is produced by radon progeny on the housing of the dose rate instruments. The effect of the radon effect largely depends on the ability of surfaces to absorb radon progeny [ 72].

Most likely, the use of air conditioning due to increase hit wave will cause higher radon consulting as a result of decrease air exchange rates, particularly in tightly sealed homes. Consequently the use of AC will be longer and will create a close house condition (EPA).

It is reported that the concentration of Radon in higher in the basement than in other rooms. Increase temperature will increase the potential to move to cooler places in the house where the radon exposure is higher (basement). This was demonstrated in a retrospective study among women in Iowa [ 73].

Locations such as homes, schools or office building have generally higher concentration of Radon than outdoor, especially in new buildings which are more energy efficient

Climate change related factors, such as high temperature, rainfall. would irrefutably influence radon exposure. Increase rainfall as observed recently, will increase radon emanation by capping the soil outdoor and directing it toward the unsaturated soil near or

under house. In case the soil are not saturated low and moderate levels of soil moisture provide a greater radon source that can enter through the holes in the buildings.

In all likelihood, the primary weather factors influencing soil-gas radon concentrations are precipitation and barometric pressure, with lesser effects attributed to temperature and, possibly, wind. The characters and composition of the soil are highly significant in determining the magnitude and extent of the soil’s response to weather change. Obviously meteorological conditions have a marked effect on radon transport in soils. Of all natural occurrences, the most important factors appear to be precipitation -by affecting soil moisture conditions-, and barometric pressure. To less extend, temperature and wind have less impactful effects, and there are conflicting observations in the literature concerning these factors.

Determining the influence of individual weather factors and their effects on radon migration and concentration in soils could be ostensibly complicated for the simple reason that several weather factors are change constantly. For example, storms are genuinely associated with precipitation, lower barometric pressure, lower temperatures and oftentimes, wind. Comparing plots of these factors with soil-gas radon concentrations would be helpful to lead to the conclusion that all of these factors cause soil-gas radon concentrations to increase [ 74].

It is commonly accepted now that we should reduce our energy consumption to mitigate the release of greenhouse gases. This observation leads prima facie to the building of energy efficiency houses. Nonetheless these new houses, which are more toughly sealed, are allowing radon gas to build up to greater degree. This double-edged sword needs to be approached and handle cautiously to find the middle way. For example, by regular measurement of radon.

Residential radon is responsible for 10-15% of the 157.400 lung cancer death occurring annually in the US [ 75]. Studies (including 7148 people with lung cancer and 14 208 control. Among controls, the percentage who were lifelong non-smokers increased as radon concentration increased. The available radon measurements covered a mean of 23 years show appreciable hazards from residential radon, particularly for smokers and recent ex-smokers, and indicate that it is responsible for about 2% of all deaths from cancer in Europe [ 76].

Radon is present in homes. According to a report from EPA from 1994 radon enters our house by different routes:

• The radon content of the soil

• The difference in pressure between the interior of the home and the soil

• The air exchange rate in the home

• The moisture content surrounding the home

• The presence and size of entry routes

As known all these 5 factors could be affected by climate change.

Radon content of the soil and climate change.

High energy costs and climate-change mitigation efforts are creating pressures to decrease ventilation rates in buildings as a means of reducing the energy used to cool or warm indoor air.

The Watras incident :

On December 2, 1984, a case of Stanley. J Watras, a construction engineer at the Limerick nuclear power in Pottstown in Pennsylvania, gained national interest. A radiation monitor was installed at the plant which was still under construction, to ensure that workers were not accidently expose to unsafe and toxic radiation levels from the plant. One day, Stanley Watras entered the plant and set off the radiation alarm. He has a high level of radiation although the plant was still in construction and was not yet filled with nuclear fuel yet. The origin of mister Watras radiation was a conundrum. Later a team of specialist relievedly discover that Watras was not picking up the radiation at the plant but from his house where the level of radon was 700 times higher than the maximum level considered safe [ 77].

The international Agency for Research on Cancer has classified 4 groups of agents according to their hazardous carcinogenic effect to humans.

• Group 1: Carcinogenic to humans: 120 agents

• Group 2A: Probably carcinogenic to humans: 82 agents

• Group 2B: Possibly carcinogenic to humans: 311 agents

• Group 3: Not classifiable as to its carcinogenicity to humans: 499 agents • Group 4: Probably not carcinogenic to humans: 1 agent

Radon is a class 1 carcinogen, which means that the evidences are strong that it causes cancer. Most people do not know that radon is the second leading cause of lung cancer in the United States, resulting in approximately 21,000 lung cancer deaths in the US each year and 11.000 deaths in UK.

There are other climate change related factors which could lead to lung cancer. High levels of indoor air pollution and fine particulates may increase the risk of lung cancer. Increased precipitation or flooding has the potential to increase the release of toxic chemical and heavy metal leaching from storage sites. Exposure to chemicals that are present in the environment may also increase, if runoff enters the water supply.

It is no secret at all, that climate change has caused last years an increase of ambient temperatures that we will witness more frequently in the near future. As result, the transfer of volatile and semi-volatile compounds from water and waste will increase, altering the distribution of contaminants to places more distant from the sources, changing subsequent human exposures [ 78].

Air pollution and cancer :

“Every breath you take contains atoms forged in the blistering furnaces deep inside stars [ 79].

In the morning of December 1952, resident of London woke up with a fog which enveloped all London and residents did not give too much attention to the fog as it happened every now and then. But over the course of few days the conditions deteriorated leading to the death of initially thought 4000, and later adjusted to 12.000 and the hospitalization of 150.000 people. Supposedly, the fog could have been cause by emissions from coal burning. This fog has led to the he passages of the Clean Air Act in 1956. But the origin and explanation of this 5 days black smog remained for years a mystery. It is only in 2016 that a team of researchers has deciphered the mystery through laboratory experiments and atmospheric measurements in China, as sulfate I big contributor to the smog, sulfuric acid particles were formed from sulfur dioxide released by coal burning for residential use and power plants, and other means. sulfur dioxide was turned into sulfuric acid. The results from this team showed that this process was facilitated by nitrogen dioxide, another co-product of coal burning. Another key aspect in the conversion of sulfur dioxide to sulfate is that it produces acidic particles, which subsequently inhibits this process. Natural fog contained larger particles of several tens of micrometers in size, and the acid formed was sufficiently diluted. Evaporation of those fog particles, then left smaller acidic haze

particles that covered the city”. This happened recurrently in china. The study shows that similar chemistry occurs frequently in China, which has battled air pollution for decades. “The difference in China is that the haze starts from much smaller nanoparticles, and the sulfate formation process is only possible with ammonia to neutralize the particles [ 80].

In the online version of the independent from 25 February 2016 Fiona Osgun wondered: “Air Pollution; How strong is the link to cancer? [ 81]. She based her article on the report of the Royal College of Physicians and the Royal College of Paediatrics and Child Health form the Royal Physicians highlighting the role of air pollution. About eight in every 100 cases of lung cancer each year in the UK are attributable to PM2.5 air pollution exposure, which is equal to approximately 3,500 people. We do not know, according to the report, how the particulate matters exactly affect the lungs but the good thing is that they have suggested several steps to counteract, rather reduce the incidence of diseases caused by air pollution.

We discussed earlier the impact of climate change on health. Nevertheless, it is worthwhile to mention that there are more factors leading unquestionably to climate change and global warming that are at the same time having an impact on health. Among these factors, we could unmistakably notify air pollutant by different substances that are released in the air daily due to our daily activities. Polycyclic aromatic hydrocarbon(PAH) is among them.

Polycyclic aromatic hydrocarbons are produced from the incomplete combustion of organic material. They are a class of chemicals that occur naturally in coal, crude oil, and gasoline. They also are produced when coal, oil, gas, wood, garbage, and tobacco are burned. PAHs generated from these sources can bind to or form small particles in the air (EPA).

Their presence in the air we breathe has been significant during the past centuries due to emissions from industrial processes and energy production, motor vehicular traffic and residential heating.

Air pollution plays an important role in the process of climate change.

IARC reported that air pollutants became a carcinogenic agent since 2013. Many components of air pollutants are diesel engine exhaust, solvent meta and dust and importantly Particulate matter- including extremely small solid particles and liquid droplets-, that are formed in the air which increase the risk on lung cancer.

According to the report from the working party of Royal college Physicians and the Royal College of Paediatrics and Child Health published in 2016 and title Every breath you take, the lifelong impact of air pollution, there was 3.2 million deaths among them 223.00 lung cancer. The report is based on the review of more than 1000 scientific papers from studies on different continents. From this analysis, it could be concluded that cancer risks caused by various pollutants present in outdoor air pollution and particularly particulate matter and transportation related. It was a large epidemiologic study that included millions living in Europe, America and Asia. It is evidently established that the predominant artificial cause of outdoor pollution is transportation and stationary power.

Long-term exposure to outdoor air pollution caused the equivalent of approximately 29,000 deaths in 2008 in the UK.40. 000 deaths occur each year due to exposure on pollution. We are exposed to this damage during our entire lifetime from first of the baby in the womb through to the years of older age[ 82].

Particulate matters; size definitely matters!

Particulate matter of PM are tiny dust-like particles just millionths of a meter wide In particular, the smallest particles — less than 2.5 millionths of a meter across, known as PM2.5 — appear to be behind lung cancers caused by pollution.

Asia is considered as one of the continents where the emissions of PAH is the highest. The annual PAH emission is 290.000 tones — in China with 114.000 tons per year followed by India with 90.000 per year —, which represents 55% of the global emissions whereas the emissions in the US is calculated to be 32.000 tons per year. European countries account for only 9.5% of the total PAH emissions annually [ 83].

The emissions from PAH and their carcinogenic effect on human health, are becoming more and more studied. There are about 500 different PAH which have been found in air. Nevertheless benzopyrene, as the representative of the whole PAH, is the most studied and documented.

PAH have different origins. Industrial and mobiles such as from vehicles.

Industrial process such as coal cocking and oil refining lead to the release of PAH. According to Corinair [ 84], industrial sources of PAH contributes as much as mobiles sources. The contribution of motor vehicles, though significant in the past, is being reduced by the

introduction of three converters in cars. In the past and without converters, the emissions were 5-10 times higher than in modern cars.

Compelling data have showed the mutagenic effect of PAH by causing the mutation of P53 tumor suppressor that is one of the mutated genes in human lung cancer [ 85].

People take thousands of breaths daily, leading to a total intake of about 10 000 liters of air per day. Lungs receive the most substantial inhaled doses.

Air pollution is associated with the occurrence of different types of cancer. Lung cancer, again, is the most widespread and studied. Researchers from Hong Kong and Birmingham conducted a study that included 66280 residents from Hong Kong aged older than 65 years, who were recruited between 1998 and 2001 and followed up till 2011. Annual concentrations of PM 25 at their house were measured using satellite and fixed monitors data. The study demonstrated that for every 10 microgram per cubic meter of increase exposure to PM25, the risks of dying from any cancer was 22% higher, and 42% for digestive cancer. Mortality due to lung cancer was 36% higher. The increase was attributable to air pollution [ 86].

In 2015 outdoor air pollution killed 4.2 million people, among them 42% were due to lung cancer and other respiratory disease. PM2.5 air pollution is responsible for up to 16.5 % of the estimate 1.7 million lung caner deaths worldwide.

Ambient PM2.5 was the fifth ranking mortality risk in 2015. Exposure to it was responsible for 4.2 million deaths and 103 disability adjusted live years in 2015,( in 1990 3.5 millions) representing 7.6% of total global deaths.59% of these were is Asia [ 87].

Another study investigated the association between long term ambient PM2,5 concentrations and lung cancer among 188.699 life long never smokers from the 12 million cancer prevention study participants enrolled by the American Cancer Society in 1982 and followed up prospectively through 2008. 1100 lung cancer deaths were observed during 26 years follow up period. Each 10 microgram per meter cube increase in PM2.5 concentrations were associated with 15-27% increase in lung cancer mortality [ 88].

Additionally, an analysis of the Harvard six cities study which enrolled 8096 peoplefollowing cities: Watertown, MA; Kingston and Harriman, TN; St. Louis, MO; Steubenville, OH; Portage, Wyocena, and Pardeeville, WI; and Topeka, KS. Participants were recruited between 1974 and 1977 -, monitored for 14 to 16 yr during the 1970s and 1980s found also a positive association between PM 2.5 and lung cancer mortality. The mortality rate ratio (RR) was 1.13 (95% confidence interval [CI], 1.04–1.73) for each 10-μg/m3 increase in city-specific PM2.5 concentrations.

There were 104,243 person-15 years of follow-up and 1,364 deaths between 1974 and 1989 (Period 1) and an additional 54,735 person-8 years of follow-up and 1,368 deaths between 1990 and 1998 (Period 2; Table 1). The overall death rate was 13.1 deaths per 1,000 person-years in Period 1 and 25.0 in Period 2, reflecting the aging of this cohort. As in previous analyses, crude mortality rates were highest in Steubenville and St. Louis. Conclusively they found lung cancer mortality positively associated with average PM2.5.

The estimated effect of particulate air pollution has been shown to increase as longer exposure periods (up to 7 weeks) are considered, indicating exposures in the month(s) before death may be important.

Exposure to PM2.5 was statistically significantly associated with deaths due to cardiovascular disease, and the association with lung cancer mortality was of borderline significance. The number of nonmalignant respiratory deaths was small (although comparable to numbers for lung cancer), but the PM2.5-associated risk was positive, although weak [ 89].

The analysis is based on data collected by the American Cancer Society (ACS) as part of the Cancer Prevention Study II (CPS-II), an ongoing prospective mortality study of approximately 1.2 million adults. Participants resided in all 50 states, the District of Columbia, and Puerto Rico, and were generally friends, neighbors, or acquaintances of ACS volunteers. Enrollment was restricted to persons who were aged 30 years or older and who were members of households with at least 1 individual aged 45 years or older. This study demonstrated associations between ambient fine particulate air pollution and elevated risks of both cardiopulmonary and lung cancer mortality. Each 10-μg/m3 elevation in long-term average PM2.5 ambient concentrations was associated with approximately a 4%, 6%, and 8% increased risk of all-cause, cardiopulmonary, and lung cancer mortality, respectively, the estimated pollution effect on both cardiopulmonary and lung cancer mortality was strongest for never smokers vs former or current smokers [ 90].

There was also a positive association found between measure of black smoke concentrations and traffic intensity and lung cancer incidence in 40.114 never smokers participants in the Netherlands cohort study on diet and cancer a total of 252 lung cancer cases were observed in the 11 years follow up time period [ 91]. In this study data from ongoing Diet and cancer study, in which 120.852 subjects , aged between 55 and 69 years old living in 204 municipalities throughout the country-,were included , were used. Exposure to black smoke, nitrogene dioxide (No2), sulfur dioxide (SO2) and PM2.5 and traffic variables were analyzed. The follow up was 11.3 years.

90% of participants have lived 10 years of longer in their 1986 municipality. During 11,3 years of follow up, 2183 lung cancer cases were reported. Black smoke average concentration was 16.8, 16.6 and 16.3 microgram per meter cube for current, ex and never smokers respectively. The association was strong among never smokers whereas no association was found among the smokers.

In many parts of the world, monitoring systems for air pollutants have been installed, usually within the framework of governmental regulatory programs. The older and most extensive of these are in North America and the European Union. The pollutants most frequently monitored are:

The gases: sulfur dioxide (SO2), nitrogen

The PM indicators: total suspended particles, black smoke, PM [ 92].

According to the World health Organization, the air we breathe is laced with cancer-causing substances and is being officially classified as carcinogenic.

The International Agency for Research on Cancer (IARC) cited data indicating that in 2010, 223,000 deaths from lung cancer worldwide resulted from air pollution, and inexorably concluded there was also convincing evidence it increases the risk of bladder cancer.

Therefore, it is of significant importance to monitor and assess the impact of air pollution within a framework with clear objectives.

There are several projects which have been put in place to investigate the effects of air pollutant on health. Examples of such projects in Europe are:

The Air Pollution Exposure of Adult Urban Populations in Europe Study (EXPOLIS), European multicenter study for measurement of air pollution exposures of working age urban population during workdays. The selected urban areas are Athens, Basel, Grenoble, Helsinki, Milan and Prague. The main objectives of EXPOLIS are: - To assess the exposures of European urban populations to major air pollutants. - To analyse the personal and environmental determinants and interrelationships to these exposures. - To develop an European database for simulation of air pollution exposures.

The Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air Study (ULTRA). It is a European collaborative project which aims to improve knowledge on

human exposure to ambient air particulate matter of different sizes and different chemical composition in Europe, and to evaluate the associated health risks.

The Relationship between Ultrafine and Fine Particulate Matter in Indoor and Outdoor Air Project (RUPIOH), The study intends to improve exposure assessment for ultra-fine particles and assess the effect of improved exposure characterization on estimated health effects. Measurements of particle number counts; The results from this study show that improved filtration is warranted in mechanically ventilated buildings, particularly for ultrafine particles, and that nighttime infiltration is significant depending on the building design [ 93].

The Chemical and Biological Characterization of Ambient Air Coarse, Fine and Ultrafine Particles for Human Health Risk Assessment Project (PAMCHAR)

The Air Pollution and Inflammatory Response in Myocardial Infarction Survivors Gene–Environment Interactions in a High-Risk Group Project (AIRGENE)

The International Agency for Research on Cancer (IARC) has put in place a list of Group 1 carcinogens which included benzene, diesel exhaust, benzo[a]pyrene (a polycyclic aromatic hydrocarbon [PAH]), indoor emissions from coal combustion, and 1,3-butadiene. Combustion-related sources, such as automobiles, indoor heating and cooking, are widespread and could lead to high potential exposures and health risks. Combustion is the reaction between a fuel and oxidant accompanied by the release of heat: Fuel + Oxidant → Products + Heat [ 94].

Discussion and Conclusion

What have we learned? Or has my effort been in vain? There are doubtlessly numerous and heterogeneous factors which could be linked to these culprits. However, I have purposely decided to draw the most attention on sun, radon, air pollution, cancer and ultimately, prevention and regulatory actions.

Beyond the shadow of a doubt, it is clearly scientifically established and agreed that excessive sun exposure increase the risk of skin cancer. Nevertheless, the sun is a known source of vitamin D which at the same time reduces the risk of breast cancer. A meta-analysis – with 68 studies published between 1998 and 2018-, including all papers published with keywords breast cancer and vitamin D showed that there is a protective relationship between circulating vitamin D and breast cancer development, in premenopausal women [ 95].

A large population-based case-control study published a year earlier, showed that women who spent a lot of time outdoors, had a lower risk of breast cancer than those who spent very short periods of time outdoors. A combined solar vitamin D score*, including all the variables related to vitamin D production, was significantly associated with reduced breast cancer risk. Vitamin D is produced in the skin through the conversion of 7-dehydrocholesterol to previtamin D3 following sufficient exposure to ultraviolet B (UV-B)

radiation from sunlight. A total of 4,352 households with eligible women were identified, and 3,420 women completed the study (79%). The majority of study participants resided in the Greater Toronto Area [ 96].

One might then ask how much sun is too much and how much sun is enough? In point of fact, the quintessential question is about adequately quantifying and regulating sun exposure. How much of sun exposure would reduce the risk on skin cancer and how much of sun exposure will protect against breast cancer by increasing the production of vitamin D from the sunlight? The temperatures are rising and according to the expectation, the summer will be longer with shorter winter leading to increase sunlight and sun exposure. For this reason, it is paramount to clearly determine the recommended duration of sun exposure that is favorable for reducing the risk of breast cancer and hazardous for skin cancer. This advice will cinch our decision as to how long we need to enjoy the sun. I would strongly recommend this topic in the program of the next meeting of the international conferences on UV and skin cancer prevention and Euroskin6.

I asked to one of my best friends and one of my multiple nephews as to whether they ever heard about radon. Their answer was placidly, but not shockingly, no!

Radon is the second cause of lung cancer after tobacco and the 7th the cause of cancer related deaths. Though the safe levels of radon varies according to the countries, high radon

concentrations can be reduced in existing houses at moderate cost, and low concentrations can usually be achieved at reasonable or low cost when new buildings are constructed. Residential radon produces substantial hazards, particularly among smokers, even at concentrations below the action levels currently recommended in many countries [ 76].

Air pollution contributes to lung cancer incidence. Ambient PM2.5 was the fifth ranking mortality risk in 2015. Exposure to it was responsible for 4.2 million deaths and 103 disability adjusted live years in 2015. Nonetheless most people spend around 85% of their time indoors and it is recognized that a significant portion of total personal exposure to particulate matter (PM) occurs in indoor environments. Roughly 80% of the time indoors is spent in residences, while the other 20% is spent in offices, restaurants, schools, and other indoor locations that are mostly mechanically ventilated buildings [ 97].

Also here, quantify the time spent are outside, despite the presence of PM, which is less risky for us is in the domain of science fiction. Nonetheless making the air less polluted is realistic once we finally “get” it.

We all know someone who knows someone who knows someone who unfortunately died from cancer. Interestingly in my 15 years of drug discovery and research in oncology, I am often unsurprisingly asked two questions at birthdays parties, with friends or while meeting new people: Do you think that cancer will be cured one day? And whether cancer has essentially to do with what we eat or breath. Never been asked what should be doing to prevent cancer. No often I have been asked about the modifiable causes of cancer. Let alone about cancer and climate change. I am sure that if we know more about the causes of cancer, we will comprehensibly do more to prevent it. The level of preventive actions varies, according to our own beliefs and, noteworthy, are based on a kind of universal wisdom. My brother in law told me this morning that he eats only biological products since years to prevent cancer and other cardiovascular diseases. There is somehow, at different levels and in various households, a kind of conscientization about the cause and effect relationship but at the same time, unconscious ignorance about prevention.

With the discovery of new molecules with new mode of action, the better understanding of cancer biology and the early detection of cancer, by virtue of diverse screening programs, the survival rates are without fail improving. According to American Cancer Society, the incidence rate as well as the mortality rate from major cancer types, namely Lung, breast, prostate, and colorectal cancer, in the US has declined steadily over the past 20 years. As of 2015, the cancer death rate, for men and women combined, had fallen 26% from its peak in 1991. This decline translates to nearly 2.4 million deaths averted during this time period [ 98].

In the annual report to the nation on the status on cancer, published in cancer in 2018 it was translucently mentioned that cancer incidence for all cancer sites combined is declining. Particularly, lung cancer, breast cancer, prostate cancer and colorectal cancer [ 99].

The continuous decline due to lung and bronchus cancer since the early 1990 among men and since the early 2000s among women is attributable to the reduction in cigarette smoking over the past 5 decades [ 100].

Lamentably, progress in declining did not occur for some other type of cancer such as skin cancer. In contrast, the incidence of skin cancer due to increase recreational exposure to the sun- longer fall, spring and high temperature in summer-, is increasing [ 101]. Therefore, as it is undoubtedly recognized, the decline of lung cancer is attributable to the reduction of tobacco consumption, the decline of skin cancer will occur only when we will significantly reduce the recreational sun exposure, in light of the global warming that is characterized by increased temperatures. On the other hand, as it has been demonstrated that the blamed global warming could be reversible, it is recommendable, unrelentingly to put our effort together to reduce the global warming which, consequently, will reduce the sun exposure and by proxi, skin cancer.

The crucial question of climate change and health is an existential one and it required self-improvement in our ways on thinking and doing. Ralph Waldo Emerson- father of existentialist ethics of self-improvement. -, taught us to “not go where the path may lead, go instead where there is no path and leave a trail (…) Every wall is a door”. The wall set up by the climate change is unbearably thick, within which we are all prisoners. Prisoners of a crime committed by others? No, by all of ours. But I am still convinced that we are, together and if well organized, able to successfully find a door. We should pressingly find the door; the remedy, but most importantly and fundamentally, the courage. Nothing has been achieved without courage and bravery and it will take more time assuredly to do right. ” Human progress never rolls in on wheels of inevitability; it comes through the tireless efforts of people (…). We must use time creatively, in the knowledge that the time is always ripe to do right” [ 102].

Many diseases such as the Plague, have been eradicated from our planet in the last century. Would we be able to rid of cancer? To cure cancer or to eradicate all men related risk factors-environmental factors causing cancer? Honestly, I don’t know. Cancer involves the mutations of many genes and even when successfully treated, the activation of dormant resistant genes would help the cancer cells to be treatment resistant, leading in the most cases, to fatal progression-outcome. The path is perilously long, the goal far; very far; but impossible is nothing and giving up is not and never been an option.

“We can rid ourselves of cancer, then only as much as we can rid ourselves of the process in our physiology that depend on growth-aging, regeneration, healing, reproduction” [ 103].

Al Gore in “Our choice” competently told us that: “not too many years from now, a new generation will look back at us in this hour of choosing and ask one or two questions Either they will ask,” What were you thinking? Didn’t you see the entire North Polar ice cap, melting before your eyes? Didn’t you hear the warnings from the scientists? Where you distracted? Did you not care?

Or they will ask instead, “how did you find the moral courage to rise up and solve a crisis so many said was impossible to solve?” We must choose which of these questions we want to answer, and we must give our answer now- not in words but in actions.”

Al Gore, here is my answer, in action, to mitigate the baleful consequences of climate change! The change in climate we constantly talk about is niggardly looming us though some might still believe that it is an apocryphal story.

As it was the case for lung cancer after the correlation with tobacco was established for the first time by Doll and Hill in 1950, despite the dismay of the majority of the people including Evarts Graham himself, who was involved in the first research work, climate change and cancer are still facing denial and dismay [ 104].

Evarts Graham together with Wynder were one of the first to establish determinately and inescapably the relationship between smoking and tobacco use. Beside pneumonectomy, beyond recall, “Smoking and Cancer” is one of the most cherished legacy of Evarts Graham. He stated that “academic investigators could provide data about risks and argue incessantly about proof and causality, but the solution had to be political”. It is in 2019, applicable for the causality between climate change and health, in particular between climate change and cancer. More policies should be developed to prevent the depletion of stratospheric ozone whereby reducing assuredly sun exposure related skin cancer.

How about radon exposure in other countries then the US. Is there any regulation? Which regulations are existent in Europe, especially when we build energy efficiency buildings? How would we create energy efficiency house which would not increase the emanation of radon decays and progenity? How should we more efficiently fight against air pollution by reducing industrial and mobile pollution. Drive an electric car, bike, take public transportation; they recommend to us.

Beginning of 2019, Australia recorded its hottest month ever in January with average temperature exceeding 30 degrees and the Midwest of the US is having one of the worst cold ever in decades because of the polar vortex.

Climate change is a fact!

It is urgent to act!

In light of provided evidences and witnessed and acknowledged threats, we can no longer ignore climate change and his impact on health. Who should be blamed?

The time to incessantly search for scapegoats is over. The culprit is in our daily actions. The solution should be in our daily thinking and action. We are all responsible and we should all together find the solutions.

Hans Rosling in Factfulness [105] - which Bill Gates consider as “one of the important books he has ever read” introduced 10 instincts which distressingly biases our views on the world and on those with whom we interact daily: he notably named: The gap instinct, the negativity instinct, the straight line instinct, the fear instinct, the size instinct, the generalization instinct, the destiny instinct, the single perspective instinct , the blame instinct and the urgency instinct. Among all these multifarious instincts, the blame instinct would be mostly applicable to all of us in relation to the worldwide destroying situation and his distorted perception. According to Hans Rosling: “The instinct to find guilty party derails our ability to develop a true, fact based understanding of the world: it steals our focus as we obsess about someone to blame, then blocks our leaning because once we have decided who to punch in the face we stop looking for explanations elsewhere (…) To understand most of the world’s significant problems we have to look beyond a guilty individual and to the system” [ 106].

It is only with tenacious courage and urgency instinct we will be able to relinquish a clean earth to the next generation. It is only with a herculean courage that we could realize our dream of eradicating cancer by reducing the impact of climate change. Hans Rosling again comes to our help by emphasizing that solving climate change challenges “requires some sense of global solidarity towards the needs of different people on different income levels.” [107]

There are several personalities in the history of the mankind who had showed his courage, whose action had had impact on billion of people. Owing to her courage and firmness, her pugnacity and intelligence, her brightness and perseverance, her perspicacity and essentially her self-abnegation and humility; her discovery had had impact on the lives of billion people. Her history will impactfully fascinate me lifelong: Marie Sklodowska Curie, first women to win a Nobel prize, first women to win two Nobel prizes. I could not finish this humble work without a deep and respectful thought for her. “We cannot hope to build a better world without improving the individual. Toward this end, each of us must work for his own highest development, accepting at the same time his share of responsibility in the general life of humanity—our particular duty being to aid those to whom we think we can be most useful.“[108]

As in the words of Thomas Kuhn, “a paradigm shift” is imperatively required to solve the climate change problem by improving the individual. Decidedly, “We cannot solve our problems with the same thinking we used when we created them.”, warned A. Einstein. No ifs ands or buts about it, after years of indefinite and hesitant discussions, we have a lot to iron out now. A paradigm shift is required, de novo, at all levels. Individuals, policymakers, business/corporate leaders and key opinion leaders, should come together frequently and think about what we all , regardless of our origins and wealth, have in common; earth and health. I could not agree more with Ralph Waldo Emerson that “the first wealth is health “(Ralph Waldo Emerson (1883). “Essays and Lectures”, p. 972, Library of America).

The business models need to be thoroughly revisited and rethought. For instance, the economist published recently an article on 09 February 2019 with an eye-catching article : “The true about big oil and climate change” and how “even as concerns about global warming grow, energy firms are planning to increase fossil-fuel production … despite the fact that last week Chicago was colder than part of Mars.” Could these big oil firm reinvent the wheel with new business models with less impact on the earth, consequently on the climate?

We are all, these days as many others in Europe, enjoying the nice warm weather. Nonetheless do we the time to reflect about how these warm temperatures are possible in this period of the year? On 25 February 2019, The Netherlands registered the warmest 25 February ever in their meteorological history, with a maximum temperature of 18.1 degrees Celsius.

Just a while ago, I had a pleasure, on a beautiful sunny Saturday afternoon, to play tennis with my friend, his brother and his brother’s son! It was a great game.; a mingling of generations to make the Royal family jealous. At the end of the game, my friend’s brother suddenly decided to show us the remains of the tree which was cut few days ago, because, like cancer metastases, the roots were invading the neighbor’s garden! While deploring this anti-environmental palliative surgery, my attention got captured by a black limousine parked outside the garage; probably with an heavy engine and significant CO2 emission!

-“What a nice, but certainly polluting car”, I said.

My friend’s brother proudly reacted by saying that he also has an electric car in the garage, which has more ridden more kilometers than the limousine; implying ostensibly that he drives the electric car more often than the limousine. Undoubtedly, he cares more about his small electric “jewelry” and that explain as to why it was securely parked in the garage.

In 1969, the Public Health Smoking Act of 1969 required all cigarettes packaging contain the statement: WARNING: THE SURGEON GENERAL HAS DETERMINED THAT CIGARETTE SMOKING IS DANGEROUS TO YOUR HEALTH. The warnings have evolved during the last decades and pictures of cancer patients were even put on the packs.

When are we having warnings stickers/messages on polluting cars -, with a message: this car causes cancer? Or pictures of lung cancer patients on trucks or airplanes?

Awaiting the quasi unthinkable paradigm shift we, as individual will need to exigently moderate the sun exposure, imperatively avoid any action which could lead to air pollution, whereby we will be able help to prevent cancer; we shall always never forget that “sola dosis facit venenum “-It is the dose which makes the poison. Again, and always!

A Call to Action from Madrid Human Papiloma Virus: is a group of viruses that are extremely common worldwide. There are more than 100 types of HPV, of which at least 14 are cancer-causing (also known as high risk type).HPV is mainly transmitted through sexual contact and most people are infected with HPV shortly after the onset of sexual activity. Cervical cancer is caused by sexually acquired infection with certain types of HPV.Two HPV types (16 and 18) cause 70% of cervical cancers and pre-cancerous cervical lesions. There is also evidence linking HPV with cancers of the anus, vulva, vagina, penis and oropharynx. (https://www.who.int/news-room/fact-sheets/detail/human-papillomavirus-(hpv)-and-cervical-cancer).

A Call to Action from Madrid

A Call to Action from Madrid

A Call to Action from Madrid

The Global Cancer Observatory (GCO) is an interactive web-based platform presenting global cancer statistics to inform cancer control and research.

A Call to Action from Madrid

A Call to Action from Madrid

EUROSKIN is an independent non-profit making scientific society, whose principal aims are to reduce the incidence and mortality of skin cancer. It sets out to achieve this through the promotion and co-ordination of collaborative actions between European professionals active in the fields of primary and/or secondary prevention. These include, for example, dermatologists, epidemiologists, biologists, physicists and other professionals with an interest in these aims. https://www.euroskin.eu/en/

A Call to Action from Madrid

A Call to Action from Madrid