A large prospective cohort study demonstrated that regular aspirin use was associated with a greater absolute reduction in colorectal cancer incidence among individuals with less healthy lifestyles. Lifestyle risk factors may help identify patients for whom aspirin use could provide a larger benefit in colorectal cancer prevention.

Published in JAMA Oncology, researchers analyzed data from 107,655 participants (63,957 women from the Nurses' Health Study and 43,698 men from the Health Professionals Follow-Up Study) for over more than 3 decades of follow-up. The mean baseline age was 49.4 years. They found that regular aspirin use (defined as ≥2 standard 325-mg tablets per week or ≥6 low-dose 81-mg tablets per week) was associated with a 10-year absolute risk reduction (ARR) of 0.97% for colorectal cancer (CRC) incidence overall.

However, the ARR varied significantly based on lifestyle factors. Among participants with the unhealthiest lifestyle scores (0-1 out of 5), the 10-year ARR with aspirin use was 1.28%, compared to just 0.11% for those with the healthiest lifestyle scores (4-5). This corresponded to a number needed to treat of 78 for the unhealthiest group versus 909 for the healthiest.

The lifestyle score incorporated body mass index (BMI), smoking, alcohol intake, physical activity, and diet quality. Among individual factors, the greatest differences in ARR were seen for BMI and smoking status.

Key findings:

• 2,544 incident CRC cases occurred over 3,038,215 person-years of follow-up
• Overall, 10-year CRC incidence: 1.98% for regular aspirin user's vs 2.95% for non-users
• 10-year ARR by lifestyle score: 1.28% for scores 0-1 (unhealthiest) 0.61% for score 2 0.65% for score 3 0.11% for scores 4-5 (healthiest)
• P<.001 for additive interaction between aspirin use and lifestyle score

The study also reported 20-year cumulative incidence data:

• Overall, 20-year CRC incidence: 4.05% for regular aspirin user's vs 5.56% for non-users
• 20-year ARR: 1.51% overall
• 20-year ARR by lifestyle score: 1.39% for scores 0-1 1.13% for score 2 1.13% for score 3 0.04% for scores 4-5

Detailed breakdown of ARR by individual lifestyle components showed:

• BMI: 1.19% ARR for BMI >25 vs 0.56% for BMI 18.5-25
• Smoking: 1.20% ARR for moderate/heavy smokers vs 0.75% for never/minimal smokers
• Alcohol: 1.08% ARR for moderate/heavy drinkers vs 0.87% for none/minimal drinkers
• Physical activity: 0.91% ARR for <30 min/day vs 0.56% for ≥30 min/day
• Diet: 0.87% ARR for <3 recommendations met vs 0.52% for ≥3 recommendations met

Notably, the relative risk reduction with aspirin use was similar across lifestyle groups. The overall hazard ratio for regular aspirin use was 0.82 (95% CI, 0.74-0.91), with HRs similar across lifestyle score strata (P=.34 for multiplicative interaction). This suggested the greater absolute benefit in unhealthy individuals stemmed from their higher baseline CRC risk.

Methods:

The study included women from the Nurses' Health Study (1980-2018) and men from the Health Professionals Follow-Up Study (1986-2018). Participants completed biennial questionnaires on aspirin use, lifestyle factors, and health outcomes. Regular aspirin users accrued 40.8% of follow-up time.

A healthy lifestyle score (0-5) was calculated based on:

• BMI 18.5-25.0
• Never smoking or <5 pack-years
• Alcohol intake ≤1 drink/day (women) or ≤2 drinks/day (men)
• ≥30 minutes/day moderate-vigorous physical activity
• Meeting ≥3 of 6 dietary recommendations

Dietary recommendations were based on adherence to World Cancer Research Fund and American Institute for Cancer Research guidelines on red meat, processed meat, dietary fiber, dairy products, whole grains, and calcium supplements.

CRC cases were confirmed through medical record review by blinded study physicians. The researchers used Cox proportional hazards models to calculate multivariable-adjusted 10-year and 20-year cumulative CRC incidence and absolute risk reductions associated with aspirin use across lifestyle groups. Models were adjusted for age, sex, BMI, alcohol intake, physical activity, diet score, family history of CRC, and endoscopic screening in the past 2 years.

Limitations included the predominantly white, health professional study population and self-reported exposure data. Adverse events from aspirin use were not systematically assessed.

The study was supported by various NIH grants and research awards. One author reported receiving personal fees from Boehringer Ingelheim, Pfizer Inc, and Freenome outside the submitted work. Full conflict of interest disclosures can be found in the original study.