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dc.contributor.authorNishihara, Reiko
dc.contributor.authorLochhead, Paul
dc.contributor.authorKuchiba, Aya
dc.contributor.authorJung, Seungyoun
dc.contributor.authorYamauchi, Mai
dc.contributor.authorLiao, Xiaoyun
dc.contributor.authorImamura, Yu
dc.contributor.authorQian, Zhi Rong
dc.contributor.authorMorikawa, Teppei
dc.contributor.authorWang, Molin
dc.contributor.authorSpiegelman, Donna
dc.contributor.authorCho, Eunyoung
dc.contributor.authorGiovannucci, Edward
dc.contributor.authorFuchs, Charles
dc.contributor.authorChan, Andrew
dc.contributor.authorOgino, Shuji
dc.date.accessioned2019-09-21T16:10:43Z
dc.date.issued2013
dc.identifier.citationNishihara, Reiko, Paul Lochhead, Aya Kuchiba, Seungyoun Jung, Mai Yamauchi, Xiaoyun Liao, Yu Imamura, et al. 2013. “Aspirin Use and Risk of Colorectal Cancer According to BRAF Mutation Status.” JAMA 309 (24): 2563. https://doi.org/10.1001/jama.2013.6599.
dc.identifier.issn0098-7484
dc.identifier.issn1538-3598
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41384653*
dc.description.abstractImportance Aspirin use reduces the risk of colorectal carcinoma. Experimental evidence implicates a role of RAF kinases in up-regulation of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2), suggesting that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin than BRAF-wild-type neoplastic cells. Objective: To examine whether the association of aspirin intake with colorectal cancer risk differs according to status of tumor BRAF oncogene mutation. Design and Setting: We collected biennial questionnaire data on aspirin use and followed up participants in the Nurses' Health Study (from 1980) and the Health Professionals Follow-up Study (from 1986) until July 1, 2006, for cancer incidence and until January 1, 2012, for cancer mortality. Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute hazard ratios (HRs) for colorectal carcinoma incidence according to BRAF mutation status. Main Outcomes and Measures Incidence of colorectal cancer cases according to tumor BRAF mutation status. Results: Among 127 865 individuals, with 3 165 985 person-years of follow-up, we 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 (multivariable HR, 0.73; 95% CI, 0.64 to 0.83; age-adjusted incidence rate difference [RD], -9.7; 95% CI, -12.6 to -6.7 per 100 000 person-years). This association was observed 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 (multivariable HR, 1.03; 95% CI, 0.76 to 1.38; age-adjusted, incidence RD, 0.7; 95% CI, -0.3 to 1.7 per 100 000 person-years: P for heterogeneity = .037, between BRAF-wild-type vs BRAF-mutated cancer risks). 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 (multivariable HR, 0.43; 95% CI, 0.25 to 0.75; age-adjusted incidence RD, -19.8; 95% CI, -26.3 to -13.3 per 100 000 person-years). The relationship between the number of aspirin tablets per week and colorectal cancer risk differed significantly by BRAF mutation status (P for heterogeneity = .005). Conclusions: and Relevance 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.
dc.language.isoen_US
dc.publisherAmerican Medical Association
dash.licenseOAP
dc.titleAspirin Use and Risk of Colorectal Cancer According to BRAF Mutation Status
dc.typeJournal Article
dc.description.versionAccepted Manuscript
dc.relation.journalJAMA - The Journal of the American Medical Association
dash.depositing.authorSpiegelman, Donna::37eeac21962b33e4e46e7aedde542849::600
dc.date.available2019-09-21T16:10:43Z
dash.workflow.comments1Science Serial ID 51007
dc.identifier.doi10.1001/jama.2013.6599
dash.source.volume309;24
dash.source.page2563


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