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Aspirin use and risk of colorectal cancer according to BRAF mutation status

This week's issue of the Journal of the American Medical Association investigates the aspirin use and risk of colorectal cancer according to BRAF mutation status.

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Aspirin use reduces the risk of colorectal carcinoma.

Experimental evidence implicates a role of RAF kinases in up-regulation of prostaglandin-endoperoxide synthase 2, suggesting that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin than BRAF–wild-type neoplastic cells.

Dr Reiko Nishihara and colleagues examined whether the association of aspirin intake with colorectal cancer risk differs according to status of tumor BRAF oncogene mutation.

The team collected biennial questionnaire data on aspirin use and followed up participants in the Nurses' Health Study and the Health Professionals Follow-up Study until 2006, for cancer incidence and until 2012, for cancer mortality.

Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute hazard ratios for colorectal carcinoma incidence according to BRAF mutation status.

The team's main outcomes and measures included incidence of colorectal cancer cases according to tumor BRAF mutation status.

Regular aspirin use was associated with lower BRAF–wild-type cancer risk
Journal of the American Medical Association

Among 127,865 individuals, with 3,165,985 person-years of follow-up, the team identified 1226 incident rectal and colon cancers with available molecular data.

Compared with nonuse, regular aspirin use was associated with lower BRAF–wild-type cancer risk.

The team observed this association irrespective of status of tumor PTGS2 expression or PIK3CA or KRAS mutation.

In contrast, regular aspirin use was not associated with a lower risk of BRAF-mutated cancer.

Compared with no aspirin use, aspirin use of more than 14 tablets per week was associated with a lower risk of BRAF–wild-type cancer.

The research team found that the relationship between the number of aspirin tablets per week and colorectal cancer risk differed significantly by BRAF mutation status.

Dr Nishihara's team concludes, "Regular aspirin use was associated with lower risk of BRAF–wild-type colorectal cancer but not with BRAF-mutated cancer risk."

"These findings suggest that BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin."

"Given the modest absolute risk difference, further investigations are necessary to determine clinical implications of our findings."

JAMA 2013; 309(24): 2563-2571
26 June 2013

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