Association between breast cancer and thyroid cancer risk: a two-sample Mendelian randomization study

Hong Tan; Sisi Wang; Feifei Huang; Zhongyi Tong

doi:10.3389/fendo.2023.1138149

Association between breast cancer and thyroid cancer risk: a two-sample Mendelian randomization study

Front Endocrinol (Lausanne). 2023 May 23:14:1138149. doi: 10.3389/fendo.2023.1138149. eCollection 2023.

Authors

Hong Tan^{1

2}, Sisi Wang³, Feifei Huang⁴, Zhongyi Tong^{1

2}

Affiliations

¹ Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Medical Laboratory, Brain Hospital of Hunan Province (The Second People's Hospital of Hunan Province), Changsha, Hunan, China.
⁴ Department of Pathology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.

Abstract

Background: Breast and thyroid cancer are increasingly prevalent, but it remains unclear whether the observed associations are due to heightened medical surveillance or intrinsic etiological factors. Observational studies are vulnerable to residual confounding, reverse causality, and bias, which can compromise causal inference. In this study, we employed a two-sample Mendelian randomization (MR) analysis to establish a causal link between breast cancer and heightened thyroid cancer risk.

Methods: We obtained the single nucleotide polymorphisms (SNPs) associated with breast cancer from a genome-wide association study (GWAS) conducted by the Breast Cancer Association Consortium (BCAC). The FinnGen consortium's latest and largest accessible GWAS thyroid cancer data at the summary level. We performed four MR analyses, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, and weighted mode, to evaluate the potential causal connection between genetically predicted breast cancer and higher risk for thyroid cancer. Sensitivity analysis, heterogeneity and pleiotropy tests were used to ensure the reliability of our findings.

Results: Our study revealed causal relationship between genetically predicted breast cancer and thyroid cancer (IVW method, odds ratio (OR) = 1.135, 95% confidence interval (CI): 1.006 to 1.279, P = 0.038). However, there was no causal association between genetically predicted triple-negative breast cancer and thyroid cancer (OR = 0.817, 95% CI: 0.610 to 1.095, P = 0.177). There was no directional pleiotropy or horizontal pleiotropy in the present study.

Conclusion: This two-sample MR study supports a causal link between ER-positive breast cancer and heightened the risk of thyroid cancer. Our analysis did not reveal a direct correlation between triple-negative breast cancer and thyroid cancer.

Keywords: Mendelian randomization; breast cancer; causal effect; single nucleotide polymorphism; thyroid cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Reproducibility of Results
Thyroid Neoplasms* / epidemiology
Thyroid Neoplasms* / genetics
Triple Negative Breast Neoplasms*

Grants and funding

This work was supported by funding from the National Natural Science Foundation of China (81501708) and the Natural Science Foundation of Hunan Province, China (Grant No. 2021JJ30956, No. 2019JJ50857).