Causal Associations of Obstructive Sleep Apnea With Cancer Risk: A Mendelian Randomization Study

Background

Observational studies have associated obstructive sleep apnea (OSA) with a higher risk of various cancers; however, causal relationships have not yet been definitively established.

Methods

Our study evaluated the causal impact of OSA on the risk of developing 22 different types of cancer using univariable and multivariable Mendelian randomization (MR). OSA-associated genetic instruments were obtained from the FinnGen study, which incorporates 38,998 OSA individuals and 336,659 non-OSA individuals from European descent. Summary-level data for 22 site-specific cancers were estimated from large genetic consortia and UK Biobank. We used inverse-variance weighting (IVW) as the primary analysis, along with several sensitivity analyses.

Results

Univariable MR analyses indicated a causal relationship of genetic susceptibility to OSA on an increased risk of Barrett's esophagus (BE) and esophageal cancer (odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.07−1.62, p = 0.01), endometrial cancer (OR = 1.36, 95% CI = 1.16−1.60, p = 2.26E-04), and its endometrioid subtype (OR = 1.28, 95% CI = 1.04−1.59, p = 0.02). Multivariable MR, accounting for possible confounders like drinking and smoking, confirmed the causal relationships of OSA on BE and esophageal cancer, and endometrial cancer.

Conclusions

This study provided evidence regarding causal associations of OSA with higher risk of BE and esophageal cancer, and endometrial cancer.