Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study.
PLoS Genet
; 18(1): e1009887, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-35061662
ABSTRACT
Morning-preference chronotype has been found to be protective against breast and prostate cancer. Sex hormones have been implicated in relation to chronotype and the development of both cancers. This study aimed to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer using a Mendelian Randomization (MR) framework. Genetic variants associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin, and oestradiol) (p<5×10-8) were obtained from published genome-wide association studies (n≤244,207 females and n≤205,527 males). These variants were used to investigate causal relationships with breast (nCases/nControls = 133,384/113,789) and prostate (nCases/nControls = 79,148/61,106) cancer using univariable, bidirectional and multivariable MR. In females, we found evidence for I) Reduced risk of breast cancer per category increase in morning-preference (OR = 0.93, 95% CI0. 88, 1.00); II) Increased risk of breast cancer per SD increase in bioavailable testosterone (OR = 1.10, 95% CI 1.01, 1.19) and total testosterone (OR = 1.15, 95% CI1.07, 1.23); III) Bidirectional effects between morning-preference and both bioavailable and total testosterone (e.g. mean SD difference in bioavailable testosterone = -0.08, 95% CI-0.12, -0.05 per category increase in morning-preference vs difference in morning-preference category = -0.04, 95% CI -0.08, 0.00 per SD increase in bioavailable testosterone). In males, we found evidence for I) Reduced risk of prostate cancer per category increase in morning-preference (OR = 0.90, 95% CI 0.83, 0.97) and II) Increased risk of prostate cancer per SD increase in bioavailable testosterone (OR = 1.22, 95% CI 1.08, 1.37). No bidirectional effects were found between morning-preference and testosterone in males. While testosterone levels were causally implicated with both chronotype and cancer, there was inconsistent evidence for testosterone as a mediator of the relationship. The protective effect of morning-preference on both breast and prostate cancer is clinically interesting, although it may be difficult to effectively modify chronotype. Further studies are needed to investigate other potentially modifiable intermediates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Hormônios Esteroides Gonadais
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Neoplasias da Mama
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Polimorfismo de Nucleotídeo Único
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Análise da Randomização Mendeliana
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
PLoS Genet
Assunto da revista:
GENETICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido