For people at high genetic risk of colorectal cancer, lifestyle changes have a particularly strong impact. According to a large study, a healthy lifestyle lowers the risk by 40% in this population - more than in people without a family history of high risk.
Whoever has "bad genes" cannot save much with modifiable risk factors for colorectal carcinoma? Quite the opposite, say the authors of an elaborate 'UK Biobank' study with data from 346.3 thousand participants.1-3
The prospective, population-based study is one of the few to quantify the interactions between lifestyle and genetic susceptibility to colorectal cancer.
For the analysis, lifestyle scores were formed according to which a classification into unhealthy, intermediate and healthy lifestyle was made. These Healthy Lifestyle Scores (HLS) included 8 factors, following the guidelines of the American Cancer Society (BMI, waist-to-hip ratio, physical activity, sedentary time, processed and red meat intake, vegetable and fruit intake, alcohol and tobacco consumption).
In addition, a polygenic risk score (PRS) was created using 95 genetic variants that have been linked to colorectal cancer risk in genome-wide association studies in recent years.
During a median follow-up of almost 6 years, the researchers identified 2,066 new cases. Healthier lifestyle scores were associated with a lower likelihood of developing colorectal cancer in a dose-response curve, with the risk reduction being more pronounced in people with a high genetic risk than in those with a low genetic risk: The authors estimate that adherence to a healthy lifestyle is associated with a nearly 40% reduction in the risk of developing the disease in people with a genetic predisposition. In people with a low genetic risk, on the other hand, it was 25%.
In other words, people aged 40 to 75 with unfavourable genetics and an unhealthy lifestyle were three times more likely to develop colorectal cancer than people with low genetic risk and a healthy lifestyle (6.4% versus 2.09%).
An important limitation of the study is that the collection of healthy lifestyle scores relied exclusively on a self-response questionnaire. This may have led to classification errors in the exposure estimation. It is likely that the extent of risk reduction was rather underestimated by this.
Moreover, even though the design as an observational study does not allow conclusions to be drawn about causality, the results suggest that lifestyle factors are once again significantly more important in people with higher genetic susceptibility than in people with low genetic risk.
References:
1. Healthy Lifestyle Changes More Beneficial to Prevent CRC for People With High Versus Low Genetic Risk. Cancer Network https://www.cancernetwork.com/view/healthy-lifestyle-changes-more-beneficial-to-prevent-crc-for-people-with-high-versus-low-genetic-risk.
2. Choi, J., Jia, G., Wen, W., Shu, X.-O. & Zheng, W. Healthy lifestyles, genetic modifiers, and colorectal cancer risk: a prospective cohort study in the UK Biobank. The American Journal of Clinical Nutrition 113, 810-820 (2021).
3. People at high genetic risk for colorectal cancer benefit more from lifestyle changes. Scienmag: Latest Science and Health News https://scienmag.com/people-at-high-genetic-risk-for-colorectal-cancer-benefit-more-from-lifestyle-changes/.