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

Dongqing Gu; Mingshuang Tang; Yutong Wang; Huijie Cui; Min Zhang; Ye Bai; Ziqian Zeng; Yunhua Tan; Xin Wang; Ben Zhang

doi:10.3389/fonc.2022.829248

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

Front Oncol. 2022 Feb 14:12:829248. doi: 10.3389/fonc.2022.829248. eCollection 2022.

Authors

Dongqing Gu¹, Mingshuang Tang¹, Yutong Wang¹, Huijie Cui², Min Zhang³, Ye Bai³, Ziqian Zeng¹, Yunhua Tan¹, Xin Wang², Ben Zhang¹

Affiliations

¹ Department of Epidemiology and Biostatistics, First Affiliated Hospital, Army Medical University, Chongqing, China.
² Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
³ School of Public Health and Management, Chongqing Medical University, Chongqing, China.

Abstract

Background: Prostate cancer is the second most common cancer in males worldwide, and multitudes of factors have been reported to be associated with prostate cancer risk.

Objectives: We aim to conduct the phenome-wide exposed-omics analysis of the risk factors for prostate cancer and verify the causal associations between them.

Methods: We 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.

Results: We 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.

Conclusions: Our 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.

Keywords: Mendelian randomization; causal relationship; prostate cancer; risk factor; systematic review.