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

Biological models suggest that obstructive sleep apnea (OSA) is potentially carcinogenic. We aimed to clarify the inconsistent epidemiological literature by considering various traditional and novel OSA severity indices.We systematically searched PubMed, Embase, Scopus, and the 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 with participants with no/mild OSA. Two reviewers independently selected studies, extracted data, and evaluated study bias using the Newcastle-Ottawa scale and quality of evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). We performed inverse variance-weighted, random-effects meta-analyses and sensitivity analyses.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 < 90%), patients with OSA who had moderate (T90 > 1.2%, hazard ratio [HR] = 1.28, 95% confidence interval [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 multiple 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-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.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.Registry: PROSPERO; URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220836; Identifier: CRD42021220836.Tan BKJ, Teo YH, Tan NKW, et al. Association of obstructive sleep apnea and nocturnal hypoxemia with all-cancer incidence and mortality: a systematic review and meta-analysis. J Clin Sleep Med. 2022;18(5):1427-1440.