Polygenic risk score, healthy lifestyle score, and colorectal cancer risk: a prospective cohort study.

Abstract

Both genetic factors and lifestyle play a critical role in colorectal cancer (CRC), but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unclear. We included 51,171 participants from the PLCO cohort. A polygenic risk score was created based on 205 genetic variants associated with CRC, 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 CRC incidence. 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 CRC (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 CRC. Moreover, participants with a high genetic risk and a favorable lifestyle had a 45% lower risk of CRC than those with a high genetic risk and an unfavorable lifestyle, with their 10-year absolute risks of 1.29% and 2.07%, respectively. Our findings suggest that adherence to a healthy lifestyle holds promise to reduce the genetic impact on CRC risk. This study indicates that modifiable lifestyle play an important role in CRC prevention, providing new insights for personalized prevention strategies.