Xie Huajie, Xi Zhihui, Wen Suqi, Zhang WenRunbei, Liu Yongfeng, Zheng Jiabin, Feng Huolun, Wu Deqing, Li Yong
Guangdong Medical University, Zhanjiang, 524000, China.
Department of Gastrointestinal Surgery, Department of Genral Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
J Epidemiol Glob Health. 2025 Apr 10;15(1):57. doi: 10.1007/s44197-025-00399-6.
Sleep problems are common in the general population, with evidence suggesting a link between circadian rhythm disruptions and various health outcomes. However, the role of chronotype in influencing colorectal cancer (CRC) risk, particularly in conjunction with genetic predisposition, remains unclear and warrants further investigation.
We analyzed data from 295,729 UK Biobank participants, among whom 4305 developed colorectal cancer. Chronotype was self-reported as morning or evening type, and a polygenic risk score for chronotype was generated from 316 genome-wide significant SNPs using 23andMe effect sizes to reduce overlap bias. Colorectal cancer risk was estimated using Cox proportional hazards models adjusted for age, sex, smoking, alcohol consumption, and the Townsend index.
Late chronotype and high polygenic risk were independently associated with an increased risk of CRC. Compared to participants with an early chronotype, those with a late chronotype exhibited a 6.5% increased risk of CRC [HR 1.065, P = 0.046]. Similarly, individuals in the high genetic risk group had a 11.0% increased risk compared with those in the low genetic risk group [HR, 1.110, P = 0.032]. Stratified analyses revealed that individuals with an intermediate genetic risk who had a late chronotype showed a 17.6% higher risk of CRC [OR, 1.176, P = 0.004], whereas those with a high genetic risk had a 25.3% increase [OR, 1.253, P = 0.001]. Through analyzing the combined effects of chronotype and PRS, we found that among individuals with an early chronotype, those with intermediate PRS had a 15.4% increased risk of CRC [HR, 1.154, P = 0.005], and those with high PRS had a 14.7% increased risk [HR, 1.147, P = 0.027].
Our findings highlight the importance of considering circadian rhythm patterns and genetic predispositions when assessing CRC risk, suggesting that chronotype may be associated with CRC risk, but further studies are needed to integrate objective circadian measurements.
睡眠问题在普通人群中很常见，有证据表明昼夜节律紊乱与各种健康结果之间存在联系。然而，生物钟类型在影响结直肠癌（CRC）风险方面的作用，特别是与遗传易感性相结合时，仍不清楚，值得进一步研究。
我们分析了来自295729名英国生物银行参与者的数据，其中4305人患了结直肠癌。生物钟类型通过自我报告分为晨型或夜型，并使用23andMe效应大小从316个全基因组显著单核苷酸多态性（SNP）生成生物钟类型的多基因风险评分，以减少重叠偏差。使用针对年龄、性别、吸烟、饮酒和汤森指数进行调整的Cox比例风险模型估计结直肠癌风险。
晚睡型生物钟和高多基因风险与结直肠癌风险增加独立相关。与晨型生物钟的参与者相比，夜型生物钟的参与者患结直肠癌的风险增加了6.5%[风险比（HR）1.065，P = 0.046]。同样，高遗传风险组的个体比低遗传风险组的个体患癌风险增加了11.0%[HR，1.110，P = 0.032]。分层分析显示，遗传风险中等且为夜型生物钟的个体患结直肠癌的风险高17.6%[比值比（OR），1.176，P = 0.004]，而高遗传风险个体的风险增加25.3%[OR，1.253，P = 0.001]。通过分析生物钟类型和多基因风险评分的综合影响，我们发现，在晨型生物钟的个体中，多基因风险评分中等的个体患结直肠癌的风险增加了15.4%[HR，1.154，P = 0.005]，多基因风险评分高的个体风险增加了14.7%[HR，1.147，P = 0.027]。
我们的研究结果强调了在评估结直肠癌风险时考虑昼夜节律模式和遗传易感性的重要性，表明生物钟类型可能与结直肠癌风险相关，但需要进一步研究以纳入客观的昼夜节律测量。
