Association of obstructive sleep apnea and nocturnal hypoxemia with all-cancer incidence and mortality: a systematic review and meta-analysis

Study objectives Biological models suggest that obstructive sleep apnea (OSA) is potentially carcinogenic. We aim to clarify the inconsistent epidemiological literature by considering various traditional and novel OSA severity indices. Methods We systematically searched PubMed, Embase, Scopus and Cochrane Library for observational or randomized studies of associations of OSA, measured by diagnostic codes or any index, each with all-cancer incidence or mortality in adults, compared to participants with no/mild OSA. Two reviewers independently selected studies, extracted data, evaluated study bias using the Newcastle-Ottawa scale and quality of evidence using GRADE. We performed inverse variance-weighted, random-effects meta-analyses and sensitivity analyses. Results We included 20 observational studies (5,340,965 participants), all with moderate/low bias, from 1,698 records. Based on T90 (sleep duration with oxygen saturation 1.2%, HR=1.28, 95%CI=1.07-1.54) and severe nocturnal hypoxemia (T90 >12%, HR=1.43, 95%CI=1.16-1.76) experienced 30-40% higher pooled all-cancer risk than normoxemic patients, after multi-adjustment for covariates including obesity. Furthermore, severe nocturnal hypoxemia nearly tripled all-cancer mortality (HR=2.66, 95%CI=1.21-5.85). Patients with apnea-hypopnea index (AHI)-defined severe OSA, but not moderate OSA, had higher all-cancer risk (HR=1.18, 95%CI=1.03-1.35) but similar all-cancer mortality as patients without OSA. An OSA diagnosis was not associated with all-cancer risk. Evidence quality ranged from low to moderate. Insufficient evidence was available on the oxygen desaturation index, lowest/median saturation and arousal index. Conclusions In patients with OSA, nocturnal hypoxemia is independently associated with all-cancer risk and mortality. Future studies should explore if risk differs by cancer type, and whether cancer screening and OSA treatment are beneficial. Systematic review registration Registry: PROSPERO; Identifier: CRD42021220836; URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220836.