孟德尔随机化
全基因组关联研究
优势比
结直肠癌
置信区间
医学
肿瘤科
遗传关联
内科学
癌症
生物
遗传学
单核苷酸多态性
基因
遗传变异
基因型
作者
Cong Meng,Liting Sun,Jinyao Shi,Li Yang,Jiale Gao,Yishan Liu,Pengyu Wei,Zhengyang Yang,Hongwei Yao,Zhong-Tao Zhang
摘要
Abstract Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two‐sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome‐wide association study (GWAS) including 14,824 European‐ancestry participants. Summary‐level data for colorectal cancer were obtained from genome‐wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL‐12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00–1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin‐12p70 levels (IL‐12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13–1.43; p < 1.22 × 10 −3 ). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02–1.35; p = .026), macrophage colony‐stimulating factor (M‐CSF) (OR: 0.85; 95% CI: 0.76–0.96; p = .005), IL‐13 (OR: 1.15; 95% CI: 1.02–1.30; p = .028), IL‐10 (OR: 1.23; 95% CI: 1.01–1.49; p = .037), and IL‐7 (OR: 1.19; 95% CI: 1.02–1.39; p = .024). Our MR studies support that one cytokine IL‐12 is significantly associated with CRC risk and that five cytokines VEGF, M‐CSF, IL‐13, IL‐10, and IL‐7 are associated with CRC risk.
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