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Causal associations of thyroid function and dysfunction with overall, breast and thyroid cancer: A two-sample
Shuai Yuan1,2, Siddhartha Kar3,4, Mathew Vithayathil5
1Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
International Journal of Cancer
|March 28, 2020
Summary
Thyroid dysfunction may causally increase breast cancer risk, particularly ER-positive tumors. Lower TSH and hypothyroidism show inverse associations with thyroid cancer, warranting further investigation into these thyroid function and cancer links.
Area of Science:
- Endocrinology and Oncology
- Genetic Epidemiology
- Cancer Etiology
Background:
- The causal relationship between thyroid dysfunction and cancer development is not well-established.
- Understanding these links is crucial for cancer prevention and management strategies.
- Previous studies have yielded inconclusive results regarding thyroid function and cancer risk.
Purpose of the Study:
- To investigate the potential causal associations between genetic predisposition to thyroid dysfunction and 22 site-specific cancers.
- To specifically examine the link between thyroid dysfunction and breast cancer risk.
- To explore the relationship between thyroid function markers and thyroid cancer incidence.
Main Methods:
- A two-sample Mendelian randomization study design was employed.
- Genetic variants associated with thyroid function (TSH, hypothyroidism, hyperthyroidism, free thyroxine) were identified from large-scale genome-wide association studies.
- Summary-level data for breast cancer and other cancers were obtained from major consortia and biobanks (e.g., Breast Cancer Association Consortium, UK Biobank).
Main Results:
- Genetically predicted thyroid dysfunction showed a causal association with increased breast cancer risk, particularly ER-positive tumors.
- Increased TSH levels and genetic predisposition to hypothyroidism were associated with decreased breast cancer risk.
- Genetic predisposition to hyperthyroidism and higher free thyroxine levels were associated with increased breast cancer risk.
- Genetically predicted TSH levels and hypothyroidism were inversely associated with thyroid cancer risk.
Conclusions:
- This study provides evidence supporting a causal role of thyroid dysfunction in breast cancer development.
- Thyroid stimulating hormone (TSH) and hypothyroidism may have protective roles against thyroid cancer.
- Further research is needed to elucidate the specific roles of TSH, hypothyroidism, and other thyroid dysfunction aspects in various cancers.
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