Yale study looks at tumor genes
It’s pretty well known that exposure to sunlight’s ultraviolet rays can cause melanoma and that smoking is strongly linked to lung cancer.
Two researchers at Yale University have made a strong genetic case for those links, as well as 22 other cancers. By looking at which mutations in our genes are likely to cause particular cancers, they can tell which are more preventable and which are more related to factors we can’t control, such as aging.
“There’s sort of a signature written in the genome of the tumor that tells you what kinds of mutations have been received in the genome,” said Jeffrey Townsend, a professor of biostatistics at the Yale School of Public Health.
While that information isn’t new, Townsend said, “We’ve managed to quantify for each site, in the genome, how much it actually contributes to the cancer.” Their study appears in the journal Molecular Biology and Evolution.
Prostate, pancreatic and thyroid cancers and gliomas are the least preventable because the genetic mutations that cause them come about mostly through aging, according to their analysis. Melanoma, lung cancer and liver cancers are those most attributable to outside factors, such as UV rays, smoking and chemical exposure, they found.
“Our work was really the synthesis of two different methods,” said Jeffrey Mandell, a co-author of the study, and a doctoral student in Yale University’s Department of Computational and Biology Informatics. “The first method being, if we’re looking at a particular cancer type, we have a bunch of patients’ tumors, and so for each patient, we try to say what mutational processes are occurring in that person.”
Our genes are made up of long strings of nucleotides, dubbed A, C, G and T for adenine, cytosine, guanine and thymine. Scientists know that a CCC string that mutates to CTC is caused by UV light, although the “letters” flanking that string also must be taken into account, according to Mandell.
Their calculations tell them at what rates the mutations are occurring. They then compare the data with which mutations contribute to a particular cancer.
“So then we do the math to combine those two pieces of information,” Mandell said. “So I’d say, given where the mutations are coming from, and how important each mutation is, how important is each process? How much is each process contributing to the path to cancer?”
Examining each form of cancer shows that there are multiple mutations in each, so that the mutation created by UV light can be found in lung cancer, head and neck cancers and ovarian cancers, among others.
But those cancers are not caused by that particular mutation.
Townsend said their work is complementary to traditional studies that link external factors such as tobacco and sunlight to cancer. “This is, I would say, even a different quality of information, because what we’re getting is an actual readout of individual tumors, where we look at the tumor and say, this is what caused those mutations,” he said. “So it’s a much more direct measurement of what’s causing them than any of that epidemiology that we’ve been doing for many, many years.”
Townsend said if the technology had been available during the lawsuits against the tobacco industry, “this would have been like a smoking gun. You look in the tumor, you see the signature of the mutations, it’s there. … How would you claim that this is not caused by smoking?”