Mendelian randomization to investigate the link between TSH and thyroid cancer.

Evidence from observational studies suggests a positive association between serum thyroid-stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause-effect relationship is poorly understood, and these studies are susceptible to bias and confounding. Using Mendelian randomization (MR) methodology, this study aimed to investigate the causal role of TSH in both benign thyr oid nodules and thyroid cancer in up to 451,025 participants in the UK Biobank. Hospita l Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test ca usal relationships between TSH and the two disease outcomes. We observed evidence of an inverse association between TSH levels and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that one standard deviation higher genetically instrumented TSH (approximately 0.8 mlU/L) resulted in an 80% reduction of risk of benign nodular disease (OR 0.20; 95% CI 0.10--0.41) and a 50% re duction of risk of thyroid cancer (OR 0.50; 95% CI 0.27--0.92). In keeping with other recen tly published studies, our results refute a causal role for TSH in both benign nodular thy roid disease and thyroid cancer, with increasing genetically instrumented TSH resulting in a lower risk of both diseases. [ABSTRACT FROM AUTHOR]