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

Area of Science:

• Oncology
• Genetics
• Epidemiology

Background:

• Increasing prevalence of breast and thyroid cancer necessitates understanding their etiological factors.
• Observational studies face challenges like confounding and bias, impacting causal inference.
• Mendelian randomization (MR) offers a robust approach to investigate causal relationships.

Purpose of the Study:

• To establish a potential causal link between breast cancer and thyroid cancer risk using a two-sample MR analysis.
• To differentiate the causal impact of specific breast cancer subtypes on thyroid cancer.
• To address limitations of observational studies in cancer etiology research.

Main Methods:

• Utilized genome-wide association study (GWAS) data for breast cancer (BCAC) and thyroid cancer (FinnGen).
• Employed four MR methods: inverse-variance-weighted (IVW), weighted median, MR-Egger, and weighted mode.
• Conducted sensitivity analyses, including heterogeneity and pleiotropy tests, to ensure result validity.

Main Results:

• A significant causal relationship was observed between genetically predicted breast cancer and increased thyroid cancer risk (IVW OR=1.135, P=0.038).
• No causal association was found between genetically predicted triple-negative breast cancer and thyroid cancer (OR=0.817, P=0.177).
• No evidence of directional or horizontal pleiotropy was detected.

Conclusions:

• The findings support a causal link between estrogen receptor-positive breast cancer and a heightened risk of thyroid cancer.
• The study did not identify a direct causal correlation between triple-negative breast cancer and thyroid cancer.
• MR analysis provides stronger evidence for the etiological relationship between specific breast cancer types and thyroid cancer.