Causal associations of thyroid function and dysfunction with overall, breast and thyroid cancer: A two-sample Mendelian randomization study.
Biological Specimen Banks
Breast Neoplasms
/ epidemiology
Female
Humans
Hyperthyroidism
/ epidemiology
Hypothyroidism
/ epidemiology
Male
Mendelian Randomization Analysis
/ methods
Polymorphism, Single Nucleotide
Thyroid Function Tests
Thyroid Gland
/ physiology
Thyroid Neoplasms
/ epidemiology
Thyrotropin
/ metabolism
Mendelian randomization
cancer
hyperthyroidism
hypothyroidism
thyroid-stimulating hormone
thyroxine
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
07
12
2019
revised:
11
02
2020
accepted:
12
03
2020
pubmed:
28
3
2020
medline:
10
4
2021
entrez:
28
3
2020
Statut:
ppublish
Résumé
Whether thyroid dysfunction plays a causal role in the development of cancer remains inconclusive. We conducted a two-sample Mendelian randomization study to investigate the associations between genetic predisposition to thyroid dysfunction and 22 site-specific cancers. Single-nucleotide polymorphisms associated with four traits of thyroid function were selected from a genome-wide association meta-analysis with up to 72,167 European-descent individuals. Summary-level data for breast cancer and 21 other cancers were extracted from the Breast Cancer Association Consortium (122,977 breast cancer cases and 105,974 controls) and UK Biobank (367,643 individuals). For breast cancer, a meta-analysis was performed using data from both sources. Genetically predicted thyroid dysfunction was associated with breast cancer, with similar patterns of associations in the Breast Cancer Association Consortium and UK Biobank. The combined odds ratios of breast cancer were 0.94 (0.91-0.98; p = 0.007) per genetically predicted one standard deviation increase in TSH levels, 0.96 (0.91-1.00; p = 0.053) for genetic predisposition to hypothyroidism, 1.04 (1.01-1.07; p = 0.005) for genetic predisposition to hyperthyroidism and 1.07 (1.02-1.12; p = 0.003) per genetically predicted one standard deviation increase in free thyroxine levels. Genetically predicted TSH levels and hypothyroidism were inversely with thyroid cancer; the odds ratios were 0.47 (0.30-0.73; p = 0.001) and 0.70 (0.51-0.98; p = 0.038), respectively. Our study provides evidence of a causal association between thyroid dysfunction and breast cancer (mainly ER-positive tumors) risk. The role of TSH and hypothyroidism for thyroid cancer and the associations between thyroid dysfunction and other cancers need further exploration.
Identifiants
pubmed: 32215913
doi: 10.1002/ijc.32988
pmc: PMC7611568
mid: EMS133103
doi:
Substances chimiques
Thyrotropin
9002-71-5
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1895-1903Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204623/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00002/7
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A19169
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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