Abstract
BACKGROUND: Thyroid and breast cancers are the two most frequent types of endocrine-related tumors among women worldwide, and their incidence is still on the rise. Observational studies have shown a relationship between thyroid and breast cancers. Nevertheless, many confounders predispose the results to interference. Accordingly, we performed a two-sample Mendelian randomization (MR) study to investigate the causal association between thyroid and breast cancers. METHODS: We acquired breast cancer data from the UK Biobank (13,879 breast cancer cases and 198,523 controls) and the Breast Cancer Association Consortium (BCAC; 122,977 breast cancer cases and 105,974 controls), and thyroid cancer data from FinnGen Biobank (989 thyroid cancer and 217,803 controls). Then, the multiplicative random effects inverse variance weighting (IVW), weight median (WM), and MR Egger methods were executed for MR analysis. RESULTS: Overall, IVW showed a causal effect of breast cancer on thyroid cancer using the BCAC dataset (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.036-1.322; P = 0.011), and this relationship was also supported by the UK Biobank dataset (OR = 23.899; 95% CI = 2.331-245.003; P = 0.007), which showed that breast cancer patients were more likely to be diagnosed with thyroid cancer. On the whole, the reverse MR analysis did not show a causal effect of breast cancer on thyroid cancer. However, IVW showed a causal effect of thyroid cancer on estrogen receptor -negative breast cancer using the BCAC dataset (OR = 1.019; 95% CI = 1.001-1.038; P = 0.043), which suggested that people with thyroid cancer were more likely to develop breast cancer. CONCLUSIONS: Breast cancer represents a possible risk factor for thyroid cancer and thyroid cancer also represents a possible risk factor for ER-negative breast cancer. Future studies using powerful genetic tools to determine the causal relationship between breast and thyroid cancers are required.