{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T06:09:30Z","timestamp":1794463770356,"version":"4.9.1"},"reference-count":56,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"Importance<\/jats:title>Aspirin reduces the risk of colorectal cancer (CRC). Identifying individuals more likely to benefit from regular aspirin use for CRC prevention is a high priority.<\/jats:p><\/jats:sec>Objective<\/jats:title>To assess whether aspirin use is associated with the risk of CRC across different lifestyle risk factors.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>A prospective cohort study among women in the Nurses\u2019 Health Study (1980-2018) and men in the Health Professionals Follow-Up Study (1986-2018) was conducted. Data analysis was performed from October 1, 2021, to May 22, 2023.<\/jats:p><\/jats:sec>Exposures<\/jats:title>A healthy lifestyle score was calculated based on body mass index, alcohol intake, physical activity, diet, and smoking with scores ranging from 0 to 5 (higher values corresponding to a healthier lifestyle). Regular aspirin use was defined as 2 or more standard tablets (325 mg) per week.<\/jats:p><\/jats:sec>Main Outcome and Measures<\/jats:title>Outcomes included multivariable-adjusted 10-year cumulative incidence of CRC, absolute risk reduction (ARR), and number needed to treat associated with regular aspirin use by lifestyle score and multivariable-adjusted hazard ratios for incident CRC across lifestyle scores.<\/jats:p><\/jats:sec>Results<\/jats:title>The mean (SD) baseline age of the 107\u202f655 study participants (63\u202f957 women from the Nurses\u2019 Health Study and 43\u202f698 men from the Health Professionals Follow-Up Study) was 49.4 (9.0) years. During 3\u202f038\u202f215 person-years of follow-up, 2544 incident cases of CRC were documented. The 10-year cumulative CRC incidence was 1.98% (95% CI, 1.44%-2.51%) among participants who regularly used aspirin compared with 2.95% (95% CI, 2.31%-3.58%) among those who did not use aspirin, corresponding to an ARR of 0.97%. The ARR associated with aspirin use was greatest among those with the unhealthiest lifestyle scores and progressively decreased with healthier lifestyle scores (P<\/jats:italic>\u2009&amp;lt;\u2009.001 for additive interaction). The 10-year ARR for lifestyle scores 0 to 1 (unhealthiest) was 1.28%. In contrast, the 10-year ARR for lifestyle scores 4 to 5 (healthiest) was 0.11%. The 10-year number needed to treat with aspirin was 78 for participants with lifestyle scores 0 to 1, 164 for score 2, 154 for score 3, and 909 for scores 4 to 5. Among the components of the healthy lifestyle score, the greatest differences in ARR associated with aspirin use were observed for body mass index and smoking.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cohort study, aspirin use was associated with a greater absolute reduction in risk of CRC among individuals with less healthy lifestyles. 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