| Title: | Early-life tobacco exposure, genetic susceptibility and incident colorectal cancer risk in UK biobank: A prospective cohort analysis |
| Journal: | Cancer Epidemiology |
| Published: | 3 Jan 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41485407/ |
| DOI: | https://doi.org/10.1016/j.canep.2025.102985 |
Publication 16886
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Abstract
BACKGROUND: Although tobacco exposure is an established risk factor for colorectal cancer (CRC), the specific impact of early-life exposure (from prenatal to adolescence) and its joints with genetic susceptibility remains uncertain. This population-based study aimed to investigate the joint effects of early-life tobacco exposure and polygenic risk on CRC.</p>
METHODS: Data from UK Biobank participants were analyzed to assess tobacco exposure during two periods: prenatal exposure (n = 429,847) and age of smoking initiation (n = 430,672). Using Cox proportional hazards models, the associations between early-life tobacco exposure and CRC incidence were explored. Additionally, we evaluated the mediating role of accelerated biological aging in the link between early-life tobacco exposure and CRC, and further integrated the polygenic risk score (PRS) to assess the joint effects of genetic on CRC risk.</p>
RESULTS: Early-life tobacco exposure exhibited age-at-initiation-dependent CRC risk associations. Smoking initiation in adolescence [hazard ratios (HR) = 1.13, 95 % confidence intervals (CI): 1.06-1.22], and adulthood (HR = 1.19, 95 % CI: 1.10-1.30) all significantly increased risk (P < 0.001), while in utero exposure and smoking initiation childhood (HR:1.06, 95 % CI: 0.94-1.19, P = 0.372) showed a suggestive but non-significant trend (HR:1.05, 95 % CI: 1.00-1.11, P = 0.066). In the joint analysis, high-PRS individuals with prenatal tobacco exposure had an elevated CRC risk compared to those with low PRS and no exposure (HR 1.28, 95 % CI: 1.16-1.42, P < 0.001). Furthermore, among high-PRS individuals, smoking initiation at any age (childhood, adolescence, or adulthood) increased CRC risk relative to never-smokers with low PRS. Mediation analysis indicated that accelerated biological aging may contribute to the association between smoking initiation at different ages and increased CRC risk.</p>
CONCLUSION: Early-life tobacco exposure elevated CRC risk, especially in genetically susceptible individuals. These findings underscored the importance of early tobacco prevention and enhanced screening for high genetic-risk populations.</p>
14 Authors
- Yu Long
- Yuting Zhu
- Meiyin Lin
- Qinming Li
- Jun Liang
- Chunyang Wang
- Ruijie Zeng
- Dongling Luo
- Lijun Zhang
- Yuyin Ma
- Chongyang Duan
- Yue Zhu
- Hao Chen
- Jianhua Liu
1 Application
| Application ID | Title |
|---|---|
| 83339 | Characterization of risk factors and biomarkers for digestive tract diseases |
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