ASPIRIN NOT EFFECTIVE FOR BRAF+ COLORECTAL CANCER PREVENTION 

More and more evidence is emerging for the colorectal cancer protection afforded by regular aspirin use. But new research has revealed that a small percentage of colorectal cancers — those that carry a certain gene mutation — might be resistant to this protection.

In a study that analyzed results from 2 large cohorts that were followed for 30 years, the link between aspirin use and risk for colorectal cancer was affected by the BRAF mutation; regular aspirin use was associated with a lower risk for wild-type BRAFcolorectal cancer (i.e., without the mutation), but not for BRAF-mutated cancer.

The research appears in the June 26 issue of JAMA.

Adds a Nuance

"This finding further supports the use of aspirin for the prevention of colorectal cancer, but adds an additional nuance, in that not all colon cancers behave the same way," study author Andrew T. Chan, MD, MPH, from the Massachusetts General Hospital in Boston, told Medscape Medical News.

"There may be colon cancers that are sensitive to the effect of aspirin and some that are resistant. This potentially opens the door for the idea that aspirin could be a method of prevention, but also that there might be specific methods by which we can target individuals for the use of aspirin," Dr. Chan said.

Experimental evidence suggests that BRAF-mutant colonic cells are less sensitive to the antitumor effects of aspirin than wild-type BRAF neoplastic cells.

In their study, Dr. Chan and colleagues sought to examine whether the association between aspirin intake and colorectal cancer risk differed according to BRAF mutation status.

The researchers collected biennial questionnaire data on aspirin use and followed participants in the Nurses' Health Study, which began in 1980, and the Health Professionals Follow-up Study, which began in 1986, until July 1, 2006 for cancer incidence and until January 1, 2012 for cancer mortality.

From this 127,865-person cohort, 1226 incident rectal and colon cancers with molecular data were available.

The researchers found that regular aspirin use was associated with a 27% lower risk for wild-type BRAFcancer (multivariable hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.64 - 0.83).

This reduced risk was observed irrespective of the status of tumor PTGS2 expression, PIK3CAmutation, or KRAS mutation.

In contrast, regular aspirin use had no effect on the risk for BRAF-mutated cancer (multivariable HR, 1.03; 95% CI, 0.76 - 1.38).

People who reported the regular use of more than 14 aspirin tablets per week had the lowest risk for wild-type BRAF cancer. Compared with nonusers of aspirin, the risk was 57% lower (multivariable HR, 0.43; 95% CI, 0.25 - 0.75).

"The relation between the number of aspirin tablets per week and colorectal cancer risk differed significantly by BRAF mutation status," Dr. Chan noted.

Molecular Profiling Might Affect Prevention

Enhancing molecular profiling might eventually pay off in terms of cancer prevention, he added.

"We are increasingly understanding that cancers behave in different ways, and with our increasing ability to do molecular profiling of different cancers, we might find that defining molecular profiles will not only have an impact on therapy, but also on prevention. We might be able to identify specific subsets of the population that are more likely to develop a certain type of colon cancer, and either target those individuals for specific preventive interventions" or exclude those who would be unlikely to benefit, he explained.

In an accompanying editorial, Boris Pasche, MD, PhD, from the University of Alabama at Birmingham, and a JAMA contributing editor, writes that the results of this study "are likely to help tailor the use of aspirin in the prevention and treatment of colorectal cancer."

However, he points out that the population in this study is predominantly white and includes a large number of health professionals.

"This population is predominantly white: 98% of the participants in the Nurses' Health Study and 95% of participants in the Health Professionals Follow-up Study are of a non-Hispanic white ethnic background. However, black individuals have the highest incidence of colorectal cancer in the United States and represent the ethnic group for whom colorectal cancer prevention may have the greatest benefit. Therefore, it will be important to determine whether [these findings] are confirmed in black individuals," Dr. Pasche notes.

This study was funded by grants to the authors from the National Institutes of Health (NIH), the Bennett Family Fund for Targeted Therapies Research, and the National Colorectal Cancer Research Alliance. Dr. Chan reports previously serving as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, Pfizer, and Pozen. Dr. Nishihara has disclosed no relevant financial relationships. Dr. Pasche reports financial relationships with the National Cancer Institute (NCI); having served as chair for the US Department of Defense Colorectal Cancer Grant review panel; serving as a member of the Cancer Genetics study section of the NCI, as an ad hoc member of the Department of Defense Breast Cancer Review Panel, and as an ad hoc reviewer of the Cancer Genetics program of the University of Iowa Comprehensive Cancer Center in 2010; receiving awards from the NCI and the NIH; receiving payment for lectures and serving on speakers bureaus from Novartis, Amgen Vectibix, HudsonAlpha Institute, Hirslanden, University of Pennsylvania, Karmanos Cancer Institute of the University of North Carolina, and LACORE; having 2 pending patent applications; receiving book royalties; and receiving travel support from the Bioelectromagnetics Society.

JAMA. 2013;309:2563-2571 and 2598-2599. Abstract, Editorial