Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China.
Environ Int. 2021 Feb;147:106309. doi: 10.1016/j.envint.2020.106309. Epub 2020 Dec 15.
Fine particulate matter (PM) is suspected to increase the risk of colorectal cancer, but the mechanism remains unknown. We aimed to investigate the association between PM exposure, genetic variants and colorectal cancer risk in the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening trial.
We included a prospective cohort of 139,534 cancer-free individuals from 10 United States research centers with over ten years of follow-up. We used a Cox regression model to assess the association between PM exposure and colorectal cancer incidence by calculating the hazard ratio (HR) and 95% confidence interval (CI) with adjustment for potential confounders. The polygenic risk score (PRS) and genome-wide interaction analysis (GWIA) were used to evaluate the multiplicative interaction between PM exposure and genetic variants in regard to colorectal cancer risk.
After a median of 10.43 years of follow-up, 1,666 participants had been diagnosed with colorectal cancer. PM exposure was significantly associated with an increased risk of colorectal cancer (HR = 1.27; 95% CI = 1.17-1.37 per 5 μg/m increase). Five independent susceptibility loci reached statistical significance at P < 1.22 × 10 in the interaction analysis. Furthermore, a joint interaction was observed between PM exposure and the PRS based on these five loci with colorectal cancer risk (P = 3.11 × 10). The Gene Ontology analysis showed that the vascular endothelial growth factor (VEGF) receptor signaling pathway was involved in the biological process of colorectal cancer.
Our large-scale analysis has shown for the first time that long-term PM exposure potential increases colorectal cancer risk, which might be modified by genetic variants.
细颗粒物（PM）被怀疑会增加结直肠癌的风险，但具体机制尚不清楚。我们旨在探讨前列腺癌、肺癌、结肠癌和卵巢癌（PLCO）筛查试验中 PM 暴露、遗传变异与结直肠癌风险之间的关系。
我们纳入了一个来自美国 10 个研究中心的、有超过 10 年随访的、有 139534 例无癌症个体的前瞻性队列。我们使用 Cox 回归模型来评估 PM 暴露与结直肠癌发病率之间的关系，通过计算危险比（HR）和 95%置信区间（CI）来调整潜在混杂因素。多基因风险评分（PRS）和全基因组交互分析（GWIA）用于评估 PM 暴露与遗传变异之间对结直肠癌风险的相乘交互作用。
在中位数为 10.43 年的随访后，有 1666 名参与者被诊断患有结直肠癌。PM 暴露与结直肠癌风险增加显著相关（HR=1.27；每增加 5μg/m，95%CI=1.17-1.37）。在交互分析中，有五个独立的易感位点达到 P<1.22×10 的统计学意义。此外，还观察到 PM 暴露与基于这五个位点的 PRS 之间存在联合交互作用与结直肠癌风险相关（P=3.11×10）。基因本体论分析显示，血管内皮生长因子（VEGF）受体信号通路参与了结直肠癌的生物学过程。
我们的大规模分析首次表明，长期 PM 暴露可能会增加结直肠癌的风险，而这种风险可能会被遗传变异所修饰。
