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Aspirin benefit tied to gene variant, study says

NEW YORK — Aspirin’s benefit in thwarting colon cancer is driven by a gene mutation that makes tumor cells less sensitive to the drug’s effects, according to a study that may lead to personalized prevention strategies.

Developing colon cancer with a mutation of the gene BRAF was similar for both regular aspirin users and non-users, according to research published in the Journal of the American Medical Association. Regular aspirin users had a 27 percent reduced risk of developing cancer without the mutation compared with those who didn’t regularly take the drug, the study found.

The finding, one of the first to show that aspirin use doesn’t prevent colon tumors with the BRAF defect, may help guide doctors when recommending the drug’s use to prevent the disease, said Andrew Chan, a study author. More studies are needed to better understand the role aspirin plays in cancer prevention, who is most at risk and which polyps may develop into tumors with a BRAF mutation, he said.

“We’ve entered a new era in which we would potentially start to think about personalizing preventive intervention,” said Chan, an associate professor of medicine at Harvard Medical School in Boston, in a telephone interview. “That’s something we haven’t been doing so far. We’ve been really trying to develop one size fits all treatment.”

A study last year in the New England Journal of Medicine showed that the protective effect of aspirin was limited to those whose tumors had a gene defect called PIK3CA. About 20 percent of colon cancers have genetic mutations in the PIK3CA gene. That compares to 10 percent to 15 percent of cancers with a defect in the BRAF gene, Tuesday’s authors said.

Colorectal cancer is the third most commonly diagnosed malignancy in both U.S. men and women, excluding skin cancers, and the third leading cause of cancer death, according to the American Cancer Society. About 102,480 new cancers of the colon and 40,340 cases of rectal cancer will be diagnosed this year. About 50,000 people are expected to die of the disease.

Researchers in the study collected questionnaire data on aspirin use among participants of the Nurses’ Health Study and the Health Professionals Follow-up Study. Of the 127,865 people in the study, 1,226 cases of rectal and colon cancers were identified and made available for molecular data.

They found that the more aspirin participants used each week the less chance of developing cancer without the mutation compared with those who didn’t take the medication. There was no benefit in increasing aspirin use on the development of cancer with the mutated gene.

“These results identify biomarkers of response to aspirin administered either preventively or therapeutically and are likely to help tailor the use of aspirin in the prevention and treatment of colorectal cancer,” wrote Boris Pasche, a professor of medicine at the University of Alabama at Birmingham and a contributing editor for JAMA, in an accompanying editorial.

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