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. 2024 Jun:104:105175.
doi: 10.1016/j.ebiom.2024.105175. Epub 2024 Jun 1.

Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study

Heming Wang  1 , Brett M Reid  2 , Rebecca C Richmond  3 , Jacqueline M Lane  1 , Richa Saxena  4 , Brian D Gonzalez  5 , Brooke L Fridley  6 , Susan Redline  1 , Shelley S Tworoger  7 , Xuefeng Wang  8
Affiliations

Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study

Heming Wang et al. EBioMedicine. 2024 Jun.

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.

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

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Conflict of interest statement

Declaration of interests BDG reports fees from Sure Med Compliance and Elly Health. SR reports fees and support to attend an advisory meeting from Eli Lilly and unpaid leadership role as a board/group member at the National Sleep Foundation and Alliance of Sleep Apnea Partner. SST reports grants from the NIH, State of Florida, ACS, DOD and BMS, fees from Ponce Health Sciences University, Ovarian Cancer Research Alliance, UNC Lineberger Comprehensive Cancer Center and AACR, and leadership role as a board/group member at City of Hope, Alberta Cancer Center and Fred Hutchinson Cancer Center. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Analysis flowchart for investigating potential causal relations between insomnia and ovarian cancer (EOC) outcomes.
Fig. 2
Fig. 2
Iterative Mendelian Randomization and Pleiotropy (IMRP) associations between insomnia and EOC outcomes.
Fig. 3
Fig. 3
Plausible biological mechanisms linking sleep disorders to ovarian cancer.
See this image and copyright information in PMC

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