Rationale: Sleep-disordered breathing (SDB) has been associated with total and cardiovascular mortality, but an association with cancer mortality has not been studied. Results from in vitro and animal studies suggest that intermittent hypoxia promotes cancer tumor growth. Objectives: The goal of the present study was to examine whether SDB is associated with cancer mortality in a community-based sample. Methods: We used 22-year mortality follow-up data from the Wisconsin Sleep Cohort sample (n ¼ 1,522). SDB was assessed at baseline with full polysomnography. SDB was categorized using the apnea-hypopnea index (AHI) and the hypoxemia index (percent sleep time below 90% oxyhemoglobin saturation). The hazards of cancer mortality across levels of SDB severity were compared using crude and multivariate analyses. Measurements and Main Results: Adjusting for age, sex, body mass index, and smoking, SDB was associated with total and cancer mortality in a dose-response fashion. Compared with normal subjects, the adjusted relative hazards of cancer mortality were 1.1 (95% confidence interval [CI], 0.5-2.7) for mild SDB (AHI, 5-14.9), 2.0 (95% CI, 0.7-5.5) for moderate SDB (AHI, 15-29.9), and 4.8 (95% CI, 1.7-13.2) for severe SDB (AHI > 30) (P-trend ¼ 0.0052). For categories of increasing severity of the hypoxemia index, the corresponding relative hazards were 1.6 (95% CI, 0.6-4.4), 2.9 (95% CI, 0.9-9.8), and 8.6 (95% CI, 2.6-28.7). Conclusions: Our study suggests that baseline SDB is associated with increased cancer mortality in a community-based sample. Future studies that replicate our findings and look at the association between sleep apnea and survival after cancer diagnosis are needed.Keywords: cancer; cohort study; mortality; obstructive sleep apnea; sleep-disordered breathing Sleep disordered breathing (SDB) is characterized by recurrent episodes of total or partial obstruction of the upper airway (apnea or hypopnea) during sleep that are associated with intermittent hypoxemia, repeated sleep disruption, and snoring (1). The prevalence of moderate to severe SDB has been estimated to be as high as 6% among U.S. adults and rising as the prevalence of obesity, a major risk factor for SDB, continues to increase (2-4). SDB is associated with a variety of psychopathological disorders (depression, reduced quality of life) and increased risk of occupational and motor vehicle injuries, as well as with a variety of cardiovascular disease outcomes, hypertension, and the metabolic syndrome (3, 5, 6). These associations have been explained by the profound metabolic and sympathetic system disruption associated with repeated hypoxemic events (6, 7).Chronic hypoxia, a common feature in solid tumor tissue, has been associated with therapeutic resistance, tumor progression, and metastatic potential (8-10). In vitro studies have further demonstrated that cultured lung cancer cells subject to intermittent hypoxia are more resistant to radiation and apoptosis and are more prone to metastasis (11).Recent results from a study using a mouse...