LAUSR

Background: Thyroid cancer (TC) is one of the endocrine tumors of which incidence rates have shown an upward trend worldwide. Obesity, another endemic health issue, has been recently reported in the association with increased TC risk. We attempted to examine if there is a causal association between body mass index (BMI) and TC using a Mendelian randomization approach. Methods: Total 17,935 healthy individuals from the Korean Genome Epidemiology Study and 1,214 TC cases from National Cancer Center, Korea, and Seoul National University Hospital were selected with age, sex, BMI, and genetic information. Based on the thirteen previously reported single nucleotide polymorphisms associated with BMI, we constructed a genetic risk score (GRS) as a genetic instrumental variable (IV) representing BMI independent of possible confounding. IV analysis was performed using the ratio (or, Wald) method to test causal association. Results: The odds of TC were 2.6 times higher in females than males. The cases were younger than the controls. The F-statistic from the regression of BMI on BMI GRS (IV) was 157.2 (usually, F larger than 10 indicates a strong and valid IV), and the IV explained 1.10% of the phenotypic variance for BMI. From IV analysis, genetically instrumented BMI was not associated with TC risk (causal odds ratio per 1kg/m2 increase in BMI 0.98 [0.79 - 1.20 95% confidence interval]). Conclusion: Our analysis suggests that positive association between obesity and TC risk repeatedly reported from several meta-analyses may be null. Further investigation is needed as the incidence rates differ in different ethnicity. Citation Format: Jeongseon Kim, Soo Ji Lee, Quy N. Nguyen, Jeonghee Lee, Eun Kyung Lee, Yul Hwangbo, Joohon Sung. Body mass index may not have causal association with thyroid cancer risk: A Mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5269.