Polygenic Risk Score, Healthy Lifestyle Score, and Colorectal Cancer Risk: A Prospective Cohort Study.

BACKGROUND

Both genetic factors and lifestyle play a critical role in colorectal cancer, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unclear.

METHODS

We included 51,171 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer cohort. A polygenic risk score was created based on 205 genetic variants associated with colorectal cancer, and a healthy lifestyle score was constructed based on six lifestyle factors. Cox regression models were used to evaluate the association of genetic and lifestyle factors with colorectal cancer incidence.

RESULTS

Compared with individuals at low genetic risk (the lowest 20%), those with intermediate genetic risk (20%-80%) and high genetic risk (the highest 20%) had a significantly increased risk of colorectal cancer (HR = 1.71 and 2.52, respectively). Compared with participants with a favorable lifestyle (scoring 4-6), those with an unfavorable lifestyle (scoring 0 or 1) had a 47% higher risk of colorectal cancer. Moreover, participants with a high genetic risk and a favorable lifestyle had a 45% lower risk of colorectal cancer than those with a high genetic risk and an unfavorable lifestyle, with their 10-year absolute risks of 1.29% and 2.07%, respectively.

CONCLUSIONS

Our findings suggest that adherence to a healthy lifestyle holds promise to reduce the genetic impact on colorectal cancer risk.

IMPACT

This study indicates that modifiable lifestyle factors play an important role in colorectal cancer prevention, providing new insights for personalized prevention strategies.