背景:病毒感染与结直肠癌(CRC)风险之间的遗传易感性关系尚未确定。
方法:我们使用全基因组关联研究(GWAS)数据进行了双样本孟德尔随机化(MR)分析。除了传统的MR方法,我们采用了其他几种方法,包括CML,ConMix,MR-RAPS,和DIVW,全面评估因果效应。还进行了灵敏度分析以确保结果的稳健性。
结果:经过敏感性分析,与感冒疮感染易感性增加相关的SNP的存在可降低CRC的风险(OR:0.73,95%CI:0.57-0.93,P=0.01).在亚组分析中,存在与病毒性肝炎易感性增加相关的SNP(OR:0.89,95%CI:0.81-0.98,P=0.02)和传染性单核细胞增多症(OR:0.91,95%CI:0.84-0.98,P=0.02)与结肠癌风险降低相关,而麻疹病毒(OR:1.41,95%CI:1.07~1.85,P=0.01)与结肠癌风险增加相关。存在与带状疱疹易感性增加相关的SNP(OR:1.26,95%CI:1.05-1.52,P=0.01)与直肠癌风险增加相关,而传染性单核细胞增多症(OR:0.809,95%CI:0.80-0.98,P=0.02)与风险降低相关。
结论:该研究提供了不同病毒感染与CRC之间遗传易感性关联的第一个证据,增强我们对CRC病因的理解。
BACKGROUND: The genetic susceptibility association between viral infection and the risk of colorectal cancer (CRC) has not been established.
METHODS: We conducted two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. In addition to traditional MR methods, we employed several other approaches, including cML, ConMix, MR-RAPS, and dIVW, to comprehensively assess causal effects. Sensitivity analyses were also performed to ensure the robustness of the results.
RESULTS: After sensitivity analysis, presence of SNPs linked to increased susceptibility to cold sores infection was found to decrease the risk of CRC (OR: 0.73, 95% CI: 0.57-0.93, P = 0.01). In subgroup analysis, presence of SNPs linked to increased susceptibility to viral hepatitis (OR: 0.89, 95% CI: 0.81-0.98, P = 0.02) and infectious mononucleosis (OR: 0.91, 95% CI: 0.84-0.98, P = 0.02) were associated with a decreased risk of colon cancer, while measles virus (OR: 1.41, 95% CI: 1.07-1.85, P = 0.01) was associated with an increased risk of colon cancer. Presence of SNPs linked to increased susceptibility to herpes zoster (OR: 1.26, 95% CI: 1.05-1.52, P = 0.01) was associated with an increased risk of rectal cancer, while infectious mononucleosis (OR: 0.809, 95% CI: 0.80-0.98, P = 0.02) was associated with a decreased risk.
CONCLUSIONS: The study provides the first evidence of the genetic susceptibility associations between different viral infections and CRC, enhancing our understanding of the etiology of CRC.