Abstract
BackgroundThe 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.MethodsWe 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.ResultsObservationally, 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).ConclusionsContrary 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.
Highlights
The incidence of thyroid cancer is rising, and relatively little is known about modifiable risk factors for the condition
Mendelian randomization did not support a causal link for obesity with benign nodular thyroid disease or thyroid cancer, 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; confidence interval (CI), 1.11-1.90)
P values calculated using logistic regression with age, sex, smoking status, alcohol consumption, Townsend deprivation index, BMI, and T2DM as covariates. adjusted waist-hip ratio (adjWHR), waist-hip ratio (WHR) adjusted for BMI; BMI, body mass index; CI, confidence interval; HDL, high-density lipoprotein; LDL, low-density lipoprotein; OR, odds ratio; T2DM, type 2 diabetes mellitus
Summary
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. Participants The UK Biobank is a longitudinal study of 500 000 participants between the ages of 40 and 69 recruited between 2006 and 2010 [19]. Demographic and health-related information was obtained via questionnaires and interviews, and anthropometric measurements, blood pressure readings, and blood, urine, and saliva samples were taken at enrollment [20]. Genotyping was performed by Affymetrix (Santa Clara, CA) using DNA extracted from whole blood samples. Two specially designed single nucleotide polymorphism arrays with more than 95% content overlap were used: the UK Biobank Axiom array® was used for ~440 000 participants, and the UK BiLEVE Axiom array® for 50 000 participants [21]. Sample quality control was performed by removing duplicated individuals, those identified as sex mismatches, of non-European descent, or outliers of heterozygosity, with an overall proportion of samples identified as poor quality of 0.2% [22]
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