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

Jul 29, 2024Endocrine

Possible two-way genetic links between breast cancer and thyroid cancer

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Abstract

A bidirectional causal association between breast cancer and thyroid cancer was identified in European populations.

The odds of developing thyroid cancer increase by 9% with breast cancer in Europeans, with a P-value of 0.023.
Breast cancer is associated with a 26.5% increase in the risk of thyroid cancer in Europeans (P < 0.001).
In Asian populations, breast cancer susceptibility is linked to a more than twofold increase in thyroid cancer risk (P < 0.001).
A bidirectional causal relationship was observed specifically between estrogen receptor-positive breast cancer and thyroid cancer in Europeans.
No causal association was found between estrogen receptor-negative breast cancer and thyroid cancer.

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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.

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

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