Genetically vulnerable individuals benefit more from lifestyle modification in reducing CRC risk

Lifestyle modification to reduce the risk of colorectal cancer (CRC) appears more beneficial among individuals with high vs low genetic susceptibility, suggests a recent study, noting that its observational nature precludes proof of causality.

Data from 346,297 participants in the UK Biobank cohort were analysed. Healthy lifestyle scores (HLSs) were generated using eight factors, based on the American Cancer Society guidelines, and were sorted into unhealthy, intermediate, and healthy groups. A polygenic risk score (PRS) was also generated using 95 genetic risk variants identified by genome-wide association studies of CRC and categorized by tertile.

Finally, the authors used Cox models to estimate hazard ratios (HRs) and 95 percent confidence intervals (CIs) of CRC risk associated with the HLS and PRS.

A total of 2,066 incident cases of CRC were identified during a median follow-up of 5.8 years. Better HLSs correlated with a lower risk of CRC in a dose-response manner. The decrease in risk was more evident among individuals with high PRS (HR for men, 0.58, 95 percent CI, 0.43–0.79; HR for men and women combined, 0.71, 95 percent CI, 0.58–0.85) than those with low PRS.

There were no multiplicative interactions identified, but the HLS1 and PRS exhibited a significant additive interaction (p=0.04 for men; p=0.02 for both men and women).

Analyses including all participants showed that the adjusted CRC cumulative risk from age 40–75 years was 6.40 percent for individuals with high PRS/unhealthy HLS1, with a relative excess risk due to interaction of 0.58 (95 percent CI, 0.06–1.10), relative to 2.09 percent among those with low PRS/healthy HLS1.

“This pattern was more apparent among those who reported not having received any bowel screening before baseline,” the authors said.