Investigating the relationship between depression and breast cancer: observational and genetic analyses.
BMC Med
; 21(1): 170, 2023 05 04.
Article
em En
| MEDLINE
| ID: mdl-37143087
ABSTRACT
BACKGROUND:
Both depression and breast cancer (BC) contribute to a substantial global burden of morbidity and mortality among women, and previous studies have observed a potential depression-BC link. We aimed to comprehensively characterize the phenotypic and genetic relationships between depression and BC.METHODS:
We first evaluated phenotypic association using longitudinal follow-up data from the UK Biobank (N = 250,294). We then investigated genetic relationships leveraging summary statistics from the hitherto largest genome-wide association study of European individuals conducted for depression (N = 500,199), BC (N = 247,173), and its subtypes based on the status of estrogen receptor (ER + N = 175,475; ER - N = 127,442).RESULTS:
Observational analysis suggested an increased hazard of BC in depression patients (HR = 1.10, 95%CIs = 0.95-1.26). A positive genetic correlation between depression and overall BC was observed ([Formula see text] = 0.08, P = 3.00 × 10-4), consistent across ER + ([Formula see text] = 0.06, P = 6.30 × 10-3) and ER - subtypes ([Formula see text] = 0.08, P = 7.20 × 10-3). Several specific genomic regions showed evidence of local genetic correlation, including one locus at 9q31.2, and four loci at, or close, to 6p22.1. Cross-trait meta-analysis identified 17 pleiotropic loci shared between depression and BC. TWAS analysis revealed five shared genes. Bi-directional Mendelian randomization suggested risk of depression was causally associated with risk of overall BC (OR = 1.12, 95%Cis = 1.04-1.19), but risk of BC was not causally associated with risk of depression.CONCLUSIONS:
Our work demonstrates a shared genetic basis, pleiotropic loci, and a putative causal relationship between depression and BC, highlighting a biological link underlying the observed phenotypic relationship; these findings may provide important implications for future studies aimed reducing BC risk.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
Tipo de estudo:
Clinical_trials
/
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Female
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Humans
Idioma:
En
Revista:
BMC Med
Assunto da revista:
MEDICINA
Ano de publicação:
2023
Tipo de documento:
Article