Appraising the Effect of Potential Risk Factors on Thyroid Cancer: A Mendelian Randomization Study

Abstract

Context: Various risk factors have been associated with the risk of thyroid cancer in observational studies. However, the causality of the risk factors is not clear given the susceptibility of confounding and reverse causation. Objective: A 2-sample Mendelian randomization approach was used to estimate the effect of potential risk factors on thyroid cancer risk. Methods: Genetic instruments to proxy 55 risk factors were identified by genome-wide association studies (GWAS). Associations of these genetic variants with thyroid cancer risk were estimated in GWAS of the FinnGen Study (989 cases and 217 803 controls). A Bonferroni-corrected threshold of P=9.09×10-4 was considered significant, and P<0.05 was considered to be suggestive of an association. Results: Telomere length was significantly associated with increased thyroid cancer risk after correction for multiple testing (OR4.68; 95% CI, 2.35-9.31; P=1.12×10-5). Suggestive associations with increased risk were noted for waist-to-hip ratio (OR1.85; 95% CI, 1.02-3.35; P=0.042) and diastolic blood pressure (OR 1.60; 95% CI, 1.08-2.38; P = 0.019). Suggestive associations were noted between hemoglobin A1c (HbA1c) (OR0.20; 95% CI, 0.05-0.82; P=0.025) and decreased risk of thyroid cancer. Risk of thyroid cancer was not associated with sex hormones and reproduction, developmental and growth, lipids, diet and lifestyle, or inflammatory factors (All P>0.05). Conclusion: Our study identified several potential targets for primary prevention of thyroid cancer, including central obesity, diastolic blood pressure, HbA1c, and telomere length, which should inform public health policy.