Genetic Risk, Lifestyle, and Colorectal Cancer Across Age at Onset: A Prospective UK Biobank Study.
4 affiliations
- 1Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.
- 2Beijing Key Laboratory of Environment and Aging, Capital Medical University, Beijing, China.
- 3Faculty of Medicine, University of Macau, Macau SAR, China.
- 4Center for Primary Health Care Research, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Abstract
Background
Polygenic risk scores (PRS) and lifestyle factors are associated with colorectal cancer (CRC), but whether their associations and joint effects vary according to age at CRC onset remains unclear. We evaluated age-related heterogeneity in the associations of genetic risk and lifestyle with CRC and examined their additive interaction in early- and late-onset CRC.Methods
We analyzed data from 405,453 cancer-free participants aged 38-73 years at baseline in the UK Biobank. PRS and a healthy lifestyle score (based on eight modifiable factors) were assessed. Age-scale Cox proportional hazards models estimated hazard ratios (HRs) for CRC risk by age at onset. Heterogeneity across age intervals was assessed using likelihood ratio tests. Additive interaction was assessed using the relative excess risk due to interaction (RERI), and differences in standardized incidence rates were evaluated.Results
During a median follow-up of 13.65 years, 6620 CRC cases were identified. Compared with low genetic risk, high genetic risk was associated with HRs of 3.72, 3.32, 2.80, and 2.01 for CRC occurring at ages < 55, 55-64, 65-74, and ≥ 75 years, respectively, with significant heterogeneity across age intervals (p for heterogeneity < 0.001). Compared with a favorable lifestyle, the corresponding HRs for an unfavorable lifestyle were 1.10, 1.50, 1.58, and 1.28, respectively, with evidence of overall heterogeneity (p for heterogeneity = 0.015). For late-onset CRC, positive additive interactions were observed for an unfavorable lifestyle combined with intermediate or high genetic risk, whereas no such interaction was detected for early-onset CRC.Conclusions
The associations of genetic susceptibility and baseline lifestyle with CRC varied according to age at onset. Positive additive interaction between genetic risk and an unfavorable lifestyle was observed for late-onset but not early-onset CRC. These findings provide further evidence that the relative and joint associations of genetic and lifestyle factors with CRC vary across the life course.
Related
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- Healthier Prediagnosis Lifestyle and Long-term Survival in Colorectal Cancer: Evidence from the Singapore Chinese Health Study
- Renin-Angiotensin System Inhibitor Use and Cancer Incidence Among UK Biobank Participants: A Prospective Cohort Study.
BibTeX
@article{sun2026genetic,
title = {{Genetic Risk, Lifestyle, and Colorectal Cancer Across Age at Onset: A Prospective UK Biobank Study.}},
author = {Wen Sun and Di Liu and Jingyang Liu and Dongxue Wang and Xiao Wang and Deqiang Zheng and Jianguang Ji},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72451},
url = {https://europepmc.org/article/MED/42958791},
note = {CC BY},
}
RIS
TY - JOUR
TI - Genetic Risk, Lifestyle, and Colorectal Cancer Across Age at Onset: A Prospective UK Biobank Study.
AU - Wen Sun
AU - Di Liu
AU - Jingyang Liu
AU - Dongxue Wang
AU - Xiao Wang
AU - Deqiang Zheng
AU - Jianguang Ji
PY - 2026
DA - 2026/10/29
JO - Cancer medicine
DO - 10.1002/cam4.72451
UR - https://europepmc.org/article/MED/42958791
AB - Background Polygenic risk scores (PRS) and lifestyle factors are associated with colorectal cancer (CRC), but whether their associations and joint effects vary according to age at CRC onset remains unclear. We evaluated age-related heterogeneity in the associations of genetic risk and lifestyle with CRC and examined their additive interaction in early- and late-onset CRC.Methods We analyzed data from 405,453 cancer-free participants aged 38-73 years at baseline in the UK Biobank. PRS and a healthy lifestyle score (based on eight modifiable factors) were assessed. Age-scale Cox proportional hazards models estimated hazard ratios (HRs) for CRC risk by age at onset. Heterogeneity across age intervals was assessed using likelihood ratio tests. Additive interaction was assessed using the relative excess risk due to interaction (RERI), and differences in standardized incidence rates were evaluated.Results During a median follow-up of 13.65 years, 6620 CRC cases were identified. Compared with low genetic risk, high genetic risk was associated with HRs of 3.72, 3.32, 2.80, and 2.01 for CRC occurring at ages < 55, 55-64, 65-74, and ≥ 75 years, respectively, with significant heterogeneity across age intervals (p for heterogeneity < 0.001). Compared with a favorable lifestyle, the corresponding HRs for an unfavorable lifestyle were 1.10, 1.50, 1.58, and 1.28, respectively, with evidence of overall heterogeneity (p for heterogeneity = 0.015). For late-onset CRC, positive additive interactions were observed for an unfavorable lifestyle combined with intermediate or high genetic risk, whereas no such interaction was detected for early-onset CRC.Conclusions The associations of genetic susceptibility and baseline lifestyle with CRC varied according to age at onset. Positive additive interaction between genetic risk and an unfavorable lifestyle was observed for late-onset but not early-onset CRC. These findings provide further evidence that the relative and joint associations of genetic and lifestyle factors with CRC vary across the life course.
SN - 2045-7634
ER -