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dc.contributor.authorCao, Yin
dc.contributor.authorNishihara, Reiko
dc.contributor.authorQian, Zhi Rong
dc.contributor.authorSong, Mingyang
dc.contributor.authorMima, Kosuke
dc.contributor.authorInamura, Kentaro
dc.contributor.authorNowak, Jonathan
dc.contributor.authorDrew, David
dc.contributor.authorLochhead, Paul
dc.contributor.authorNosho, Katsuhiko
dc.contributor.authorMorikawa, Teppei
dc.contributor.authorZhang, Xuehong
dc.contributor.authorWu, Kana
dc.contributor.authorWang, Molin
dc.contributor.authorGarrett, Wendy
dc.contributor.authorGiovannucci, Edward
dc.contributor.authorFuchs, Charles
dc.contributor.authorChan, Andrew
dc.contributor.authorOgino, Shuji
dc.date.accessioned2019-09-23T15:33:58Z
dc.date.issued2016
dc.identifier.citationCao, Yin, Reiko Nishihara, Zhi Rong Qian, Mingyang Song, Kosuke Mima, Kentaro Inamura, Jonathan A. Nowak, et al. 2016. “Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes.” Gastroenterology 151 (5): 879–892.e4. https://doi.org/10.1053/j.gastro.2016.07.030.
dc.identifier.issn0016-5085
dc.identifier.issn1528-0012
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41392036*
dc.description.abstractBACKGROUND and AIMS: Aspirin use reduces colorectal cancer risk. Aspirin, a nonsteroidal anti-inflammatory drug, inhibits prostaglandin-endoperoxide synthase 2 (PTGS2 or cyclooxygenase-2); PTGS2 promotes inflammation and suppresses T-cell-mediated adaptive immunity. We investigated whether the inverse association of aspirin use with colorectal carcinoma risk was stronger for tumors with lower degrees of lymphocytic infiltrates than for tumors with higher degrees of lymphocytic infiltrates. Methods: We collected aspirin use data biennially from participants in the Nurses' Health Study and Health Professionals Follow-up Study. Participants were asked whether they took aspirin in most weeks, the number of tablets taken per week, and years of aspirin use. We collected available tumor specimens (n = 1458) from pathology laboratories in the United States. A pathologist confirmed the diagnosis of colorectal adenocarcinoma (excluding anal squamous cell carcinoma), and evaluated histopathology features, including patterns and degrees of lymphocytic infiltrates within and around tumor areas. Person-years of follow-up evaluation were accrued from the date of return of questionnaires until dates of colorectal cancer diagnosis, death, or the end of follow-up evaluation (June 2010). Duplication-method Cox proportional hazards regression was used to assess the association of aspirin with the incidence of colorectal carcinoma subgroups according to the degree of tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral reaction, or Crohn's-like reaction. Results: We documented 1458 rectal and colon cancers. The inverse association between regular aspirin use and colorectal cancer risk significantly differed by concentrations of TILs (P-heterogeneity = .007). Compared with nonregular use, regular aspirin use was associated with a lower risk of tumors that had low levels of TILs (relative risk, 0.72; 95% confidence interval, 0.63-0.81), and strength of the association depended on aspirin dose and duration (both P-trend < .001). In contrast, aspirin use was not associated with a risk of tumors having intermediate or high levels of TILs. This differential association was consistent regardless of the status of tumor microsatellite instability, mutations in BRAF, or expression of PTGS2. Regular aspirin use was associated with a lower risk of tumors that contained low levels of CD3(+) T cells, CD8(+) T cells, or CD45RO (PTPRC)(+) T cells (measured by immunohistochemistry and computer-assisted image analysis). ConclUSIONS: Based on data from the prospective cohort studies, regular use of aspirin is associated with a lower risk of colorectal carcinomas with low concentrations of TILs. These findings indicate that the immune response in the tumor microenvironment could be involved in the chemopreventive effects of aspirin.
dc.language.isoen_US
dc.publisherElsevier
dash.licenseOAP
dc.titleRegular Aspirin Use Associates with Lower Risk of Colorectal Cancers with Low Numbers of Tumor-infiltrating Lymphocytes
dc.typeJournal Article
dc.description.versionAccepted Manuscript
dc.relation.journalGastroenterology
dash.depositing.authorGiovannucci, Edward L.::fd8dcb59a5a5859f2a85fabae12a60cf::600
dc.date.available2019-09-23T15:33:58Z
dash.workflow.comments1Science Serial ID 33680
dc.identifier.doi10.1053/j.gastro.2016.07.030
dash.source.volume151;5
dash.source.page879


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