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Aspirin cut risk of BRAF wild-type colorectal cancer.

FROM JAMA

Regular aspirin use has been linked to a lower risk of BRAF wild-type, but not BRAF mutated, colorectal cancer, according to a report.

The absolute difference in risk was considered modest, so further investigation is required to clarify the clinical implications of these study findings. But the results do indicate that BRAF status may someday serve as a marker of sensitivity to aspirin therapy, said Reiko Nishihara, Ph.D., of the Dana-Farber Cancer Institute and Harvard University, Boston, and her associates.

Activating mutations in the BRAF oncogene occur in 10%-15% of colorectal cancers, and are thought to play a role in the upregulation and synthesis of certain prostaglandins. Since aspirin is an antiprostaglandin, "we hypothesized that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin, whereas BRAF wild-type neoplastic cells might be more susceptible to its antitumor effects," they said.

The study findings also could lead to new treatment strategies that are better tailored to tumor characteristics. And they "enhance understanding of the molecular pathogenesis of colorectal neoplasia and the mechanisms through which aspirin may exert its antineoplastic effects," the investigators noted.

Dr. Nishihara and her colleagues examined the association between aspirin use and colorectal cancer's BRAF mutation status using data from two large national prospective cohort studies that tracked participants' aspirin use beginning in the 1980s. They analyzed data on 82,095 women in the Nurses' Health Study (NHS) and 45,770 men in the Health Professionals Follow-Up Study (HPFS), in which numerous dietary and other exposures were monitored in detail at 2-year intervals.

"Our detailed, updated exposure data allowed us to control for the effects of potential confounding by other dietary and lifestyle factors implicated in colorectal carcinogenesis," they said.

The study participants used aspirin primarily to prevent cardiovascular disease and to treat arthritis, other musculoskeletal pain, and headache.

During 28 years (more than 3 million person-years) of follow-up, 1,226 of these subjects developed colorectal cancer. As expected, both men and women who used aspirin regularly showed a significantly lower risk of developing the disease than did the aspirin nonusers.

DNA tissue was extracted from stored samples of tumor tissue so that BRAF status could be determined.

Aspirin use was associated with a significantly lower risk of BRAF wild-type cancer. For this type of tumor, the age-adjusted incidence was 40.2 per 100,000 person-years among the aspirin nonusers, compared with 30.5 per 100,000 person-years for aspirin users.

In contrast, use of aspirin showed no relation to the risk of BRAF-mutated cancer, for which the age-adjusted incidence was 5.0 per 100,000 person-years among nonusers and 5.7 per 100,000 among aspirin users (JAMA 2013;309:2563-71).

In a sensitivity analysis that accounted for the concomitant use of cholesterol-lowering agents, antihypertensive medications, and NSAIDs, the results were unchanged.

This study was supported by the National Institutes of Health, the Bennett Family Fund for Targeted Therapies Research, and the National Colorectal Cancer Research Alliance. Dr. Nishihara reported no financial conflicts. An associate reported ties to Bayer Healthcare, Millenium Pharmaceuticals, Pfizer, and Pozen.

Caption: Aspirin use showed no relation to the risk of BRAF-mutated cancer.

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Title Annotation:GASTROENTEROLOGY
Author:Moon, Mary Ann
Publication:Internal Medicine News
Date:Jul 1, 2013
Words:530
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