Healthy Lifestyle Changes More Beneficial to Prevent CRC for People With High Versus Low Genetic Risk


Data extrapolated from healthy lifestyle scores and polygenic risk scores found that healthy lifestyle changes were associated with a greater reduction in the risk in developing colorectal cancer for patients with a high genetic risk of disease development.

People with a high genetic risk for colorectal cancer (CRC) development could benefit more from healthy changes to their lifestyle than people with a lower genetic risk of CRC, according to data from a prospective cohort study published in The American Journal of Clinical Nutrition.1

“Using data from a large population-based cohort study, we found that adherence to a healthy lifestyle was associated with a significantly reduced risk of developing CRC, regardless of the risk determined by genetic factors,” wrote the investigators from Vanderbilt University Medical Center. “Intriguingly, the reduction in CRC risk was most evident among those at the highest genetic risk, following a greater than additive interaction model.”

Both healthy lifestyle scores (HLSs) and a polygenic risk score (PRS) were both assessed to determine their association with CRC. The HLSs incorporated 8 lifestyle factors, primarily from the guidelines set forth by the American Cancer Society, including BMI (kg/m2), waist-to-hip ratio, physical activity, sedentary time, processed and red meat intake, vegetable and fruit intake, alcohol consumption, and tobacco smoking. These factors were used to categorize the population into unhealthy, intermediate, and healthy groups.

Genome-wide association studies of CRC were used to identify 95 genetic risk variants to create the PRS. The variants were selected from the most recent studies that included large sample sizes of people of European ancestry.

The investigative team identified 2066 CRC incident cases after a median follow-up of 5.8 years. Overall, healthier HLSs were associated with a reduced risk in developing CRC, with the reduction more apparent in individuals with a high PRS compared with those with a low PRS (HR, 0.71; 95% CI, 0.58-0.85).

Focusing on the individuals aged 40 to 75 years, the research team found that those who had a high PRS and an unhealthy HLS score had a higher adjusted cumulative risk (6.40%) of CRC compared with individuals categorized with a low PRS/healthy HLS (2.09%).

“Results from this study could be useful to design personalized prevention strategies for colorectal cancer prevention,” study author, Wei Zheng, MD, PhD, MPH, Anne Potter Wilson Professor of Medicine and associate director for Population Sciences Research at Vanderbilt-Ingram Cancer Center, said in a press release.2

One limitation of the study is due to the self-reported questionnaire used for the HLS, which may have introduced some misclassification errors in exposure assessment. It’s likely that the level of risk reduction in the research is underestimated due to this limitation.

More, because the population of this research comprised patients of European descent, the generalizability of these data to other populations should be evaluated in further research. Future studies should also incorporate more of the American Cancer Society’s guidelines to fully understand the lifestyle impact on CRC risk.

“Although the observational nature of the study design precludes proof of causality, our study suggests that healthy lifestyles may reduce the risk of CRC, particularly among individuals with a genetic susceptibility,” wrote the investigators. “The benefit of lowering the risk of CRC by adherence to a healthy lifestyle is expected to be the greatest among individuals with highest genetic susceptibility, which can help establish personalized preventive strategies for cancer prevention.”


1. Choi J, Jia G, Wen W, Shu XO, Zheng W. Healthy lifestyles, genetic modifiers, and colorectal cancer risk: a prospective cohort study in the UK Biobank. Am J Clin Nutr. 2021;113(4):810-820. doi:10.1093/ajcn/nqaa404

2. People at high genetic risk for colorectal cancer benefit more from lifestyle changes. News release. Vanderbilt University Medical Center. Published May 13, 2021. Accessed May 20, 2021.

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