Document Type

Article

Publication Date

6-2024

Identifier

DOI: 10.1016/j.ebiom.2024.105175; PMCID: PMC11169961

Abstract

BACKGROUND: Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study.

METHODS: Insomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors.

FINDINGS: Insomnia was associated with higher risk of endometrioid EOC (OR = 1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR = 0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR = 1.45, 95% CI 1.13-1.87) and HGSOC (OR = 1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR = 2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors.

INTERPRETATION: This study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival.

FUNDING: National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.

Journal Title

EBioMedicine

Volume

104

First Page

105175

Last Page

105175

MeSH Keywords

Humans; Female; Mendelian Randomization Analysis; Sleep Initiation and Maintenance Disorders; Ovarian Neoplasms; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Risk Factors; Carcinoma, Ovarian Epithelial; Survival Analysis

Keywords

Epithelial ovarian cancer; Genome-wide association study; Insomnia; Mendelian randomization; Patient survival; The ovarian cancer association consortium

Comments

This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

Publisher's Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00210-X/fulltext

Download

Share

COinS