Study finds aspirin reduces colon cancer risk, with benefits varying by lifestyle factors

By Vijay Kumar MalesuReviewed by Benedette Cuffari, M.Sc.Aug 7 2024

In a recent study published in the JAMA Oncology, researchers evaluate the association between aspirin use, lifestyle factors, and the risk of colorectal cancer (CRC).

Study: Aspirin Use and Incidence of Colorectal Cancer According to Lifestyle Risk. Image Credit: Kmpzzz / Shutterstock.com

Can aspirin prevent colon cancer?

Aspirin is effective in preventing colorectal neoplasia, which is defined as abnormal cell growth in the colon or rectum. However, the long-term risks associated with chronic aspirin use limit its widespread use; therefore, personalized recommendations are needed to identify patients most likely to benefit from this treatment approach.

Several studies have shown that the anti-cancer effects of aspirin use can vary based on an individual’s diet, body mass index (BMI), and smoking habits. Thus, there remains a need for additional research to refine preventive strategies and understand the impact of aspirin on CRC risk across different lifestyle factors.

About the study

Study participants were enrolled in two prospective cohort studies, which included men from the Health Professionals Follow-Up Study (HPFS) and women from the Nurses’ Health Study (NHS). The NHS began in 1976 with 121,700 female nurses 30 to 55 years of age, whereas the HPFS began in 1986 with 51,529 male health professionals 40 to 75 years of age. Study participants with a history of cancer or inflammatory bowel disease before baseline or with missing baseline data were excluded from the study. 

Follow-up continued until the diagnosis of CRC, death, or the end of the follow-up period, which was June 30, 2018, for NHS and January 31, 2018, for HPFS. Data analyses were performed between October 1, 2021, and May 22, 2023. Over 90% of the study participants completed biennial questionnaires on diet, lifestyle, medication use, and disease outcomes, including CRC.

Data on regular aspirin use were collected every two years starting in 1980 for NHS and 1986 for HPFS. Regular aspirin use was defined as two or more standard 325 mg dose tablets or six or more low-dose tablets of 81 mg every week.

Lifestyle factors such as smoking, BMI, physical activity, alcohol intake, and diet were evaluated. A healthy lifestyle score was created based on these factors, with scores ranging from zero to five, in which higher scores indicated healthier lifestyles. 

To assess the absolute benefit of regular aspirin use by lifestyle score, multivariable-adjusted 10-year cumulative CRC incidence was calculated. Cox proportional hazards regression models were adjusted for age, lifestyle components, sex, family history of CRC, and endoscopic screening.

Absolute risk reduction (ARR) and the number needed to treat (NNT) were calculated. The analyses also considered a potential latency effect of aspirin by evaluating 20-year cumulative CRC incidence. 

Cox models estimated hazard ratios for CRC incidence by aspirin use across lifestyle scores, with multiplicative interaction evaluated through likelihood ratio tests.

Study findings 

Among the 107,655 study participants, 63,957 women from the NHS, and 43,698 men from the HPFS, 2,544 cases of incident CRC were documented over 3,038,215 person-years. About 41% of the study cohort were considered regular aspirin users. The mean baseline age was 49.4 years, with a standard deviation of nine years.

The 10-year multivariable-adjusted cumulative incidence of CRC was 2.95% among nonregular aspirin users compared to 1.98% among regular users, thus indicating an ARR of 0.97% and NNT of 103.

The ARR associated with regular aspirin use decreased progressively with higher lifestyle scores. More specifically, the 10-year ARR for aspirin users was 1.28% for participants with the unhealthiest lifestyle scores of zero or one, 0.61% for a lifestyle score of two, 0.65% for a lifestyle score of three, and 0.11% for the healthiest scores of four and five.

The 20-year multivariable-adjusted cumulative incidence of CRC indicated that nonregular aspirin users had a cumulative incidence of 5.56% compared to 4.05% among regular users, resulting in an ARR of 1.51%. The ARR associated with aspirin use decreased with higher lifestyle scores, with an overall ARR of 1.39% for participants with the lowest lifestyle scores observed compared to 0.04% for those with the highest scores.

For individual components of the healthy lifestyle score, a greater 10-year ARR was observed among participants with BMI values of 25 or more, moderate/heavy smokers, moderate/heavy alcohol users, and those who reported less physical activity and lower adherence to dietary recommendations.

Regular aspirin users were at an 18% reduced risk of incident CRC as compared to nonregular users. The relative reduction in CRC incidence was consistent across different healthy lifestyle score groups. Additionally, a supplemental analysis indicated differences in relative risk reduction by BMI and alcohol intake but not by other factors.

Conclusions

Study participants with unhealthier lifestyles experienced the most significant absolute benefit from aspirin use, especially in terms of BMI and smoking. Regular aspirin use similarly reduced CRC incidence across different lifestyle profiles.

Several different mechanisms may be involved in aspirin's protective effects against CRC, including inhibition of proinflammatory signals and modulation of antitumor responses. Despite previous broad recommendations, identifying those who would benefit most from aspirin remains essential due to the potential adverse effects of chronic aspirin use.