A mendelian randomization study of thyroid hormones and urologic cancer
Objective In this study,we conducted Mendel Randomization(MR)study to investi-gate the causal relationship between TSH,FT4 and bladder cancer,kidney cancer and prostate cancer.Methods To conduct our research,we constructed a genetic tool that included 51 and 25 single nucleo-tide polymorphisms(SNPs)(P＜5×10-8)associated with TSH and FT4,respectively,identified through genome-wide association studies.These genetic markers are derived from extensive GWAS data from the Thyroid Association.The data set of bladder cancer,kidney cancer and prostate cancer was obtained from a large GWAS.The database is based on the Genetic Epidemiology Study(GERA)of UK Biobank and Kaiser Permanente on Adult Health and Aging Cohort.The Negative Variance Weighted(IVW)method was used to estimate the causal relationship between genetic prediction of thyroid function and urinary sys-tem cancer riskResults In the analysis of bladder cancer,48 SNPs related to TSH and 19 SNPs related to FT4 were included in the MR analysis.One SNP(rs1 157994)was not available in the data set of blad-der cancer.MR analysis showed that no causal effect of genetic prediction of TSH[odds ratio(OR)=0.975,95％confidence interval(CI):0.807-1.177,P＞0.05]or FT4(OR=0.812,95％CI:0.631-1.045,P＞0.05)on the risk of bladder cancer was observed.In the analysis of renal cell carcinoma,a to-tal of 49 TSH related SNPs and 19 FT4 related SNPs were included in the MR analysis.The results showed that genetic predicted TSH(OR=0.919,95％CI:0.747-1.130,P＞0.05)or FT4(OR=1.247,95％CI:0.928-1.675,P＞0.05)had no discernible causal effect on the risk of renal cancer.In the analysis of prostate cancer,a total of 49 TSH linked SNPs and 19 FT4 related SNPs were included in MR analysis.The application of the IVW method indicated a causal relationship between thyroid stimulating hormone lev-els and low risk of prostate cancer(OR=0.927,95％CI:0.861-0.998,P＜0.05).Conclusion There is a causal relationship between thyroid hormone levels and low risk of prostate cancer.FT4 and TSH have no causal relationship with other urological cancers.
Mendelian randomizationThyroid stimulating hormonesThyroxineThyroid hormonesUrologic cancer
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