Investigation of the causal relationship between breast cancer and thyroid cancer: a set of two-sample bidirectional Mendelian randomization study.

ABSTRACT

PURPOSE: A potential association between breast (BC) and thyroid cancer (TC) has been observed. We investigated if the relationship between BC and TC is causal using bidirectional Mendelian randomization (MR) in Asian and European populations. METHODS: BC-linked single nucleotide polymorphisms (SNPs) were acquired from a genome-wide association study (GWAS) conducted by the Breast Cancer Association Consortium and Biobank Japan. The most recent TC GWAS data were obtained from the FinnGen Project and National Biobank of Korea. We assessed the potential causal relationship between BC and TC using various MR methods, including inverse-variance-weighting (IVW). Sensitivity, heterogeneity, and pleiotropic tests were performed to assess reliability. RESULTS: We found a bidirectional causal association between BC and TC within Europeans (IVW, TC on BC odds ratio [OR] 1.090, 95% confidence interval [CI] 1.012-1.173, P = 0.023; BC on TC OR 1.265, 95% CI 1.158-1.381, P < 0.001). A one-way causal relationship between BC susceptibility and TC risk was found in Asians (IVW BC on TC OR 2.274, 95% CI 2.089-2.475, P < 0.001). Subsequently, we identified a noteworthy bidirectional causal relationship between estrogen receptor (ER)-positive BC and TC (IVW, TC on ER-positive BC OR 1.104, 95% CI 1.001-1.212, P = 0.038; ER-positive BC on TC OR 1.223, 95%CI 1.072-1.395, P = 0.003), but not ER-negative BC and TC in Europeans. CONCLUSION: We revealed a reciprocal causal association between ER-positive BC and TC. These findings establish a theoretical framework for the simultaneous surveillance and treatment of BC and TC.