Smok­ing ‘causes hun­dreds of DNA changes’

Malta Independent - - HEALTH -

Smok­ing leaves an “ar­chae­o­log­i­cal record” of the hun­dreds of DNA mu­ta­tions it causes, sci­en­tists have dis­cov­ered.

Hav­ing se­quenced thou­sands of tu­mour genomes, they found a 20-a-day smoker would rack up an average of 150 mu­ta­tions in ev­ery lung cell each year.

The changes are per­ma­nent, and per­sist even if some­one gives up smok­ing.

Re­searchers say analysing tu­mour DNA may help ex­plain the un­der­ly­ing causes of other can­cers.

Pamela Pugh, 69, was di­ag­nosed with lung can­cer in 2013. She started smok­ing aged 17 and quit in her early 50s.

But she said: “Even though I gave up many years ago, the ef­fects of smok­ing caught up with me.

“Had I known as a teenager that smok­ing caused mu­ta­tions which would stay with me for life then I would never had started”.

The study, in the jour­nal Sci­ence, was car­ried out by an international group, in­clud­ing the Well­come Trust Sanger In­sti­tute in Cam­bridgeshire and the Los Alamos Na­tional Lab­o­ra­tory in New Mex­ico.

The anal­y­sis shows a di­rect link be­tween the num­ber of cig­a­rettes smoked in a life­time and the num­ber of mu­ta­tions in tu­mour DNA.

The au­thors found that, on average, smok­ing a packet of cig­a­rettes a day led to: • 150 mu­ta­tions in each lung cell

ev­ery year • 97 in the lar­ynx or voice box • 23 in the mouth • 18 in the blad­der • six in the liver

Joint lead au­thor Prof Sir Mike Strat­ton, from the Well­come Trust Sanger In­sti­tute, said: “The more mu­ta­tions there are, the higher the chance that these will oc­cur in the key genes that we call can­cer genes, which con­vert a nor­mal cell into a can­cer cell.“

The re­searchers said that in tis­sues such as the lung, which are di­rectly ex­posed to smoke, they could find the mu­ta­tional sig­na­ture of the chem­i­cals in to­bacco smoke, of which at least 60 are car­cino­gens.

How­ever, they could not find this same pat­tern in tis­sues such as the blad­der, which are not di­rectly ex­posed.

Prof Strat­ton said in these or­gans smok­ing seemed to be ac­cel­er­at­ing a nat­u­ral mu­ta­tional process, but how it did this was “mys­te­ri­ous and com­plex”.

He said the same in­ves­tiga­tive ap­proach could be used with other can­cers where the un­der­ly­ing causes were less well un­der­stood.

“By look­ing in the genomes of the can­cers, we will find the ar­chae­o­log­i­cal traces of past ex­po­sures which have been re­spon­si­ble for gen­er­at­ing the can­cers and that may po­ten­tially lead to pre­ven­tion,” he said.

Dr David Gil­li­gan, con­sul­tant on­col­o­gist at Pap­worth Hos­pi­tal and Roy Cas­tle Lung Foun­da­tion trustee, said: “For ev­ery 150 mu­ta­tions in the cell each year, that is 150 op­por­tu­ni­ties for lung can­cer to de­velop.

“Lung can­cer has been at the bot­tom of the sur­vival league for many years, but there are many ex­cit­ing de­vel­op­ments, in­clud­ing im­munother­apy and ge­net­i­cally tar­geted drug treat­ments.”

Ms Pugh has re­ceived treat­ment at Pap­worth and Ad­den­brooke’s Hos­pi­tals in Cam­bridgeshire.

She has just spent six months on a trial of a drug that aims to dis­rupt the genes that drive the growth of lung can­cer.

Par­tic­i­pants in the Ma­trix trial have DNA from their tu­mours ex­am­ined to check they have genes that may re­spond to the drug.

But a scan has shown the tu­mour in Ms Pugh’s right lung is grow­ing, and she has had to leave the trial.

She will now un­dergo more chemo­ther­apy and ra­dio­ther­apy.

There are 35,000 deaths a year in the UK from lung can­cer, and it is es­ti­mated that nine out of 10 cases are pre­ventable.

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