The Causal Relationships Between Extrinsic Exposures and Risk of Prostate Cancer: A Phenome-Wide Mendelian Randomization Study

作者全名："Gu, Dongqing; Tang, Mingshuang; Wang, Yutong; Cui, Huijie; Zhang, Min; Bai, Ye; Zeng, Ziqian; Tan, Yunhua; Wang, Xin; Zhang, Ben"

作者地址："[Gu, Dongqing; Tang, Mingshuang; Zeng, Ziqian; Tan, Yunhua; Zhang, Ben] Army Med Univ, Affiliated Hosp 1, Dept Epidemiol & Biostat, Chongqing, Peoples R China; [Cui, Huijie; Wang, Xin] Sichuan Univ, West China Sch Publ Hlth, Dept Epidemiol & Biostatist, Chengdu, Peoples R China; [Cui, Huijie; Wang, Xin] Sichuan Univ, West China Fourth Hosp, Chengdu, Peoples R China; [Zhang, Min; Bai, Ye] Chongqing Med Univ, Sch Publ Hlth & Management, Chongqing, Peoples R China"

通信作者："Zhang, B (通讯作者)，Army Med Univ, Affiliated Hosp 1, Dept Epidemiol & Biostat, Chongqing, Peoples R China."

来源：FRONTIERS IN ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000761992400001

JCR分区：Q2

影响因子：4.7

年份：2022

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：prostate cancer; Mendelian randomization; risk factor; causal relationship; systematic review

摘要："BackgroundProstate cancer is the second most common cancer in males worldwide, and multitudes of factors have been reported to be associated with prostate cancer risk. ObjectivesWe aim to conduct the phenome-wide exposed-omics analysis of the risk factors for prostate cancer and verify the causal associations between them. MethodsWe comprehensively searched published systematic reviews and meta-analyses of cohort studies and conducted another systematic review and meta-analysis of the Mendelian randomization studies investigating the associations between extrinsic exposures and prostate cancer, thus to find all of the potential risk factors for prostate cancer. Then, we launched a phenome-wide two-sample Mendelian randomization analysis to validate the potentially causal relationships using the PRACTICAL consortium and UK Biobank. ResultsWe found a total of 55 extrinsic exposures for prostate cancer risk. The causal effect of 30 potential extrinsic exposures on prostate cancer were assessed, and the results showed docosahexaenoic acid (DHA) [odds ratio (OR)=0.806, 95% confidence interval (CI): 0.661-0.984, p=0.034], insulin-like growth factor binding protein 3 (IGFBP-3) (OR=1.0002, 95%CI: 1.00004-1.0004, p=0.016), systemic lupus erythematosus (SLE) (OR=0.9993, 95%CI: 0.9986-0.99997, p=0.039), and body mass index (BMI) (OR=0.995, 95%CI: 0.990-0.9999, p=0.046) were associated with prostate cancer risk. However, no association was found between the other 26 factors and prostate cancer risk. ConclusionsOur study discovered the phenome-wide exposed-omics risk factors profile of prostate cancer, and verified that the IGFBP-3, DHA, BMI, and SLE were causally related to prostate cancer risk. The results may provide new insight into the study of the pathogenesis of prostate cancer."

基金机构："National Natural Science Foundation of China [81903393, 81903398]; Chongqing Natural Science Foundation Program [cstc2020jcyj-msxmX0021]; Chongqing Special Postdoctoral Science Foundation [XmT2018068]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (81903393, and 81903398), Chongqing Natural Science Foundation Program (cstc2020jcyj-msxmX0021), and Chongqing Special Postdoctoral Science Foundation (XmT2018068). The sponsors of this study had no role in study design, data collection, analysis, interpretation, writing of the report, or the decision for submission."