Causal relationship between thyroid dysfunction and prostate cancer： a two-sample Mendelian randomization study

Abstract:

Objective To investigate the causal relationship between thyroid dysfunction and prostate cancer by using the two-sample Mendelian randomization method.Methods Relevant genome-wide association study（GWAS） data were collected. The exposure factor was thyroid dysfunction（including hyperthyroidism，hypothyroidism），and the outcome variable was prostate cancer. We performed Mendelian randomization analysis using the inverse-variance weighted method（IVW），weighted median，and Mendelian randomization-Egger method. The heterogeneity test，sensitivity analysis，and pleiotropic analysis were also carried out.Results There was a negative causal relationship between hyperthyroidism and prostate cancer（IVW：OR=0.015，95%CI=0~0.436） and a positive causal relationship between congenital hypothyroidism and prostate cancer（IVW：OR=1.088，95%CI=1.003~1.180）. No causal relationship was found between the other types of hypothyroidism and prostate cancer. No results had pleiotropy. Leave-one-out cross-validation suggested that the results were robust.Conclusion Thyroid dysfunction is causally linked to prostate cancer，and low levels of thyroid hormones may be related to an increased risk of prostate cancer，which need further verification through Mendelian randomization studies using larger-size GWAS data.