Does Obesity Cause Thyroid Cancer? A Mendelian Randomization Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 7; pp. e2398 - e2407
• Main Authors: Fussey, Jonathan Mark, Beaumont, Robin N, Wood, Andrew R, Vaidya, Bijay, Smith, Joel, Tyrrell, Jessica
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.07.2020
• Subjects: Adiposity - genetics; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Female; Genetic Predisposition to Disease; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Obesity - epidemiology; Obesity - genetics; Online Only; Thyroid Neoplasms - epidemiology; Thyroid Neoplasms - genetics; molecular epidemiology; diabetes mellitus; type 2; thyroid neoplasms; mendelian randomization; obesity
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa250

Abstract Background The incidence of thyroid cancer is rising, and relatively little is known about modifiable risk factors for the condition. Observational studies have suggested a link between adiposity and thyroid cancer; however, these are subject to confounding and reverse causality. Here, we used data from the UK Biobank and Mendelian randomization approaches to investigate whether adiposity causes benign nodular thyroid disease and differentiated thyroid cancer. Methods We analyzed data from 379 708 unrelated participants of European ancestry in the UK Biobank and identified 1812 participants with benign nodular thyroid disease and 425 with differentiated thyroid carcinoma. We tested observational associations with measures of adiposity and type 2 diabetes mellitus. One and 2-sample Mendelian randomization approaches were used to investigate causal relationships. Results Observationally, there were positive associations between higher body mass index (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.08-1.22), higher waist-hip ratio (OR, 1.16; 95% CI, 1.09-1.23), and benign nodular thyroid disease, but not thyroid cancer. Mendelian randomization did not support a causal link for obesity with benign nodular thyroid disease or thyroid cancer, although it did provide some evidence that individuals in the highest quartile for genetic liability of type 2 diabetes had higher odds of thyroid cancer than those in the lowest quartile (OR, 1.45; CI, 1.11-1.90). Conclusions Contrary to the findings of observational studies, our results do not confirm a causal role for obesity in benign nodular thyroid disease or thyroid cancer. They do, however, suggest a link between type 2 diabetes and thyroid cancer.