Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
EBioMedicine. 2024 Jun;104:105175. doi: 10.1016/j.ebiom.2024.105175. Epub 2024 Jun 1.
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.
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.
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.
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.
National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.
失眠是上皮性卵巢癌（EOC）患者中最常见的睡眠障碍。我们通过两样本 Mendelian 随机化（MR）研究，调查了遗传预测的失眠与 EOC 风险和生存之间的因果关系。
使用英国生物库和 23andMe 的全基因组关联研究（GWAS）荟萃分析中确定的遗传变异来代理失眠。利用卵巢癌协会联盟（OCAC）GWAS 中与 EOC 风险和总生存相关的遗传关联，我们对 66450 名女性（超过 11000 例有临床随访）进行了迭代 Mendelian 随机化和多效性（IMRP）分析，随后进行了一系列敏感性分析。通过控制化疗和临床因素，估计了癌症基因组图谱（TCGA）卵巢癌研究中与生存和治疗反应相关的遗传关联。
失眠与子宫内膜样 EOC 的风险增加相关（OR=1.60，95%CI 1.05-2.45），而与高级别浆液性 EOC（HGSOC）和透明细胞性 EOC 的风险降低相关（OR=0.79 和 0.48，95%CI 0.63-1.00 和 0.27-0.86）。在生存分析中，失眠与侵袭性 EOC（OR=1.45，95%CI 1.13-1.87）和 HGSOC（OR=1.4，95%CI 1.04-1.89）的生存时间较短相关，这在调整体重指数和生殖年龄后减弱。失眠与 TCGA HGSOC 病例接受标准化疗后生存时间缩短相关（OR=2.48，95%CI 1.13-5.42），但在调整临床因素后减弱。
这项研究支持失眠对 EOC 风险和生存的影响，表明针对失眠的治疗可能对预防和提高患者生存至关重要。
美国国立卫生研究院，美国国立癌症研究所。完整的资助细节在致谢中提供。
