A new study offers a possible answer to the question “Why me?”
Cancer results from a combination of spontaneous mutations that arise with age—just call it “bad luck”—and environmental exposures to carcinogens such as tobacco, ultraviolet light or sometimes viruses. But the question of the relative contribution of luck—compared with more explicit causes—has generated vigorous debate for years.
Inside a tumor, there are usually many genetic mutations, but only a small subset of them “drive” cancerous growth. The rest are harmless “passenger” mutations. Using previous knowledge about the specific mutational patterns caused by exposures to carcinogens such as tobacco smoke or UV light, the researchers could estimate what proportion of driving mutations were caused by carcinogens and what proportion arose from accidental alterations in DNA that occur during normal cell division.
“There have been a lot of sidetracks taken over the years,” says cancer researcher and oncologist Rameen Beroukhim of the Dana-Farber Cancer Institute, who was not involved with the new study, because people assumed that frequently mutated genes in a given cancer type must be contributing to the development of the cancer—only to find out that those mutations were just passengers.
These large mutations are not negligible in cancer cell genomes: in some cancers, one out of every 10 million nucleotides undergoes a point mutation, but one of every three is involved in chromosomal rearrangements or increases in copy numbers, Beroukhim says. Still, it is unclear how much these big rearrangements contribute to cancer growth because they have yet to be quantified for individual cancers.
Townsend agrees that this context is important: in the same way, obesity, exercise or alcohol consumption may not directly cause mutations, but these factors change the metabolic environment in the body and thereby alter the risk of cancer, too. Future work will need to incorporate this larger context. Future work will also extend to more cancer types as more cancer genomes are sequenced and become available.
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