Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes.
Abstract | BACKGROUND & AIMS: 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 (Pheterogeneity = .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 Ptrend < .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.
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Authors | Yin Cao, Reiko Nishihara, Zhi Rong Qian, Mingyang Song, Kosuke Mima, Kentaro Inamura, Jonathan A Nowak, David A Drew, Paul Lochhead, Katsuhiko Nosho, Teppei Morikawa, Xuehong Zhang, Kana Wu, Molin Wang, Wendy S Garrett, Edward L Giovannucci, Charles S Fuchs, Andrew T Chan, Shuji Ogino |
Journal | Gastroenterology
(Gastroenterology)
Vol. 151
Issue 5
Pg. 879-892.e4
(11 2016)
ISSN: 1528-0012 [Electronic] United States |
PMID | 27475305
(Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Aspirin
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Topics |
- Adenocarcinoma
(immunology, prevention & control)
- Adult
- Aged
- Anti-Inflammatory Agents, Non-Steroidal
(therapeutic use)
- Aspirin
(therapeutic use)
- Colorectal Neoplasms
(immunology, prevention & control)
- Female
- Follow-Up Studies
- Humans
- Lymphocyte Count
- Lymphocytes, Tumor-Infiltrating
- Male
- Middle Aged
- Prospective Studies
- Risk
- Tumor Microenvironment
(immunology)
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