| Title: | Healthy lifestyles, genetic modifiers, and colorectal cancer risk: a prospective cohort study in the UK Biobank |
| Journal: | American Journal of Clinical Nutrition |
| Published: | 1 Apr 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33675346/ |
| DOI: | https://doi.org/10.1093/ajcn/nqaa404 |
| URL: | https://academic.oup.com/ajcn/article-pdf/113/4/810/36911623/nqaa404.pdf |
| Citations: | 44 (29 in last 2 years) as of 8 Aug 2024 |
Publication 12875
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Abstract
BACKGROUND: Both genetic and lifestyle factors play an etiologic role in colorectal cancer (CRC).</p>
OBJECTIVES: We evaluated potential gene-environment interactions in CRC risk.</p>
METHODS: We used data from 346,297 participants in the UK Biobank cohort. Healthy lifestyle scores (HLSs) were constructed using 8 lifestyle factors, primarily according to the American Cancer Society guidelines, and were categorized into unhealthy, intermediate, and healthy groups. A polygenic risk score (PRS) was created using 95 genetic risk variants identified by genome-wide association studies of CRC and was categorized by tertile. Cox models were used to estimate the HRs and 95% CIs of CRC risk associated with the HLS and PRS.</p>
RESULTS: During a median follow-up of 5.8 y, 2066 incident cases of CRC were identified. Healthier HLSs were associated with reduced risk of CRC in a dose-response manner. The risk reduction was more apparent among those with high PRS (HRhealthy vs. unhealthy HLS1: 0.58; 95% CI: 0.43, 0.79 for men and 0.71; 0.58, 0.85 for men and women combined) than those with low PRS. Although no multiplicative interactions were identified, the HLS1 and PRS showed a significant additive interaction (P = 0.02 for all participants combined, 0.04 for men). In analyses including all participants, the adjusted CRC cumulative risk from age 40 to 75 y was 6.40% for those with high PRS/unhealthy HLS1, with a relative excess risk due to interaction of 0.58 (95% CI: 0.06, 1.10), compared with 2.09% among those with low PRS/healthy HLS1. This pattern was more apparent among those who reported not having received any bowel screening before baseline.</p>
CONCLUSIONS: Although the observational nature of the study precludes proof of causality, our findings suggest that individuals with a high genetic susceptibility could benefit more substantially than those with a low genetic risk from lifestyle modification in reducing CRC risk.</p>
13 Keywords
- Aged
- Cohort Studies
- Colorectal Neoplasms
- Diet
- Female
- Genetic Predisposition to Disease
- Genotype
- Healthy Lifestyle
- Humans
- Male
- Middle Aged
- Prospective Studies
- United Kingdom
5 Authors
- Jungyoon Choi
- Guochong Jia
- Wanqing Wen
- Xiao-Ou Shu
- Wei Zheng
1 Application
| Application ID | Title |
|---|---|
| 40685 | Evaluating the utility of disease polygenetic risk scores in identifying high-risk individuals using UK Biobank data |
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