时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
First, it is not well established whether the associations of polygenic susceptibility and a comprehensive lifestyle profile with CRC change systematically across multiple ages of onset rather than simply between early‐ and late‐onset diseases.；Third, although previous studies have examined joint or interactive effects of genetic and environmental factors, whether additive interaction between genetic susceptibility and a comprehensive lifestyle profile differs according to CRC age at onset remains unclear.；To address these gaps, we used a large prospective cohort from the UK Biobank to evaluate the associations of CRC PRS and an eight‐component healthy lifestyle score with incident CRC across four onset‐age intervals (< 55, 55–64, 65–74, and ≥ 75 years).
方法
Participants were selected from the UK Biobank, a population‐based prospective cohort with baseline phenotypic and genetic information.；Early‐onset CRC cases were defined as diagnosis before age 55, considering that participants in the UK Biobank tend to be healthier than the general population [] and to ensure an adequate number of cases in the younger population for our analyses [] (Figure ).；Finally, 405,453 participants aged 38–73 years were included in the primary analysis.；We used the standard CRC PRS released by the UK Biobank.
核心结论
Of these cases, 387 were diagnosed before age 55 years (204 women, 183 men) and 6233 were diagnosed at age 55 years or older (2702 women and 3531 men) (Table ).；Compared with participants at low genetic risk, those with intermediate and high genetic risk were more likely to be male, White, have a family history of CRC, have an unfavorable lifestyle, and exhibit a higher incidence of both early‐ and late‐onset CRC (Table ).；Participants who developed early‐onset CRC, compared with those with late‐onset CRC, were more likely to be female, non‐White, and have a higher proportion of high genetic risk (Table ). ‖ 结论：These findings provide further evidence that the associations of genetic susceptibility and lifestyle with CRC are age‐dependent and may inform future research on age‐specific risk stratification and prevention.
局限
This heterogeneity was primarily driven by the high versus low genetic risk contrast.；The heterogeneity was mainly attributable to the unfavorable versus favorable lifestyle contrast, particularly when comparing CRC occurring before age 55 years with CRC occurring at ages 55–64 and 65–74 years.；The present study extends this literature by evaluating genetic and comprehensive lifestyle associations across multiple onset‐age intervals, formally testing heterogeneity across age groups, and examining additive genetic and lifestyle interaction for early‐ and late‐onset CRC.
对本项目的价值
★☆☆☆☆ 相关范围内，作为背景与横向对照收录。队列：UK Biobank；最大样本量约 405,453。
全文来源
PMC JATS 全文（正文 27,608 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Genetic Risk, Lifestyle, and Colorectal Cancer Across Age at Onset: A Prospective UK Biobank Study.
- 期刊与标识：Cancer Med · PMID 42958791 · DOI 10.1002/cam4.72451
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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