@article{ab74e30bda2a48ec8c21afa59480243c,
title = "Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals",
abstract = "Although aspirin has been considered a promising agent for prevention of colorectal cancer, recent data suggest a lack of benefit among older individuals. Whether some individuals with higher risk of colorectal cancer may benefit from aspirin remains unknown. We used a 95-variant colorectal cancer polygenic risk score (PRS) to explore the association between genetic susceptibility to colorectal cancer and aspirin use in a prospective study of 12,609 individuals of European descent ages ≥70 years, enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) double-blinded, placebo-controlled randomized trial (randomized controlled trial; RCT). Cox proportional hazards models were used to assess the association of aspirin use on colorectal cancer, as well as the interaction between the PRS and aspirin treatment on colorectal cancer. Over a median of 4.7 years follow-up, 143 participants were diagnosed with incident colorectal cancer. Aspirin assignment was not associated with incidence of colorectal cancer overall [HR = 0.94; 95% confidence interval (CI), 0.68-1.30] or within strata of PRS (P for interaction = 0.97). However, the PRS was associated with an increased risk of colorectal cancer (HR = 1.28 per SD; 95% CI, 1.09-1.51). Individuals in the top quintile of the PRS distribution had an 85% higher risk compared with individuals in the bottom quintile (HR=1.85; 95%CI, 1.08-3.15). In a prospective RCT of older individuals, aPRS is associatedwith incident colorectal cancer risk, but aspirin usewas not associatedwith a reduction of incident colorectal cancer, regardless of baseline genetic risk.",
author = "Andrew Bakshi and Yin Cao and Orchard, {Suzanne G.} and Carr, {Prudence R.} and Joshi, {Amit D.} and Manning, {Alisa K.} and Buchanan, {Daniel D.} and Asad Umar and Winship, {Ingrid M.} and Peter Gibbs and Zalcberg, {John R.} and Finlay Macrae and McNeil, {John J.} and Paul Lacaze and Chan, {Andrew T.}",
note = "Funding Information: S.G. Orchard reports grants from National Insitutue on Aging, NCI, National Health and Medical Research Council of Australia; and grants from Victorian Cancer Agency, Australia during the conduct of the study. P.R. Carr reports grants from NIH, National Health and Medical Research Council of Australia, Monash University (Melbourne, Victoria, Australia), Victorian Cancer Agency; and grants from ASPREE Flagship cluster grant [including the Commonwealth Scientific and Industrial Research Organisation, Monash University, Menzies Research Institute, Australian National University (Canberra, Australia), The University of Melbourne (Melbourne, Victoria, Australia)] during the conduct of the study. A.T. Chan reports personal fees from Bayer Pharma AG during the conduct of the study; grants and personal fees from Pfizer Inc.; personal fees from Boehringer Ingelheim; and grants from Zoe outside the submitted work. No disclosures were reported by the other authors. Funding Information: This work was supported by an ASPREE Flagship cluster grant (including the Commonwealth Scientific and Industrial Research Organisation, Monash University, Menzies Research Institute, Australian National University, University of Melbourne); and grant numbers U01AG029824 (to J.J. McNeil) and U19AG062682 (to A.T. Chan and J.J. McNeil) from the National Institute on Aging and the NCI at the HNIB; by grant numbers 334047 and 1127060 (to J.J. McNeil) from the National Health and Medical Research Council of Australia, and by Monash University and the Victorian Cancer Agency. A.T. Chan is supported by an NCI Outstanding Investigator Award (R35 CA253185) and is the Stuart and Suzanne Steele MGH Research Scholar. J.J. McNeil is supported by a National Health and Medical Research Council (NHMRC) Leadership Fellowship Investigator Grant (ID: 1173690). P. Lacaze is supported by a National Heart Foundation Future Leader Fellowship (ID: 102604). Y. Cao is supported by NCI project grant number K07CA218377. Publisher Copyright: {\textcopyright} 2022 American Association for Cancer Research Inc.. All rights reserved.",
year = "2022",
month = jul,
doi = "10.1158/1940-6207.CAPR-22-0011",
language = "English",
volume = "15",
pages = "447--454",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research (AACR)",
number = "7",
}
