A large-scale Belgian study has identified a sex-specific relationship between sleep apnea and lung cancer risk in patients with chronic obstructive pulmonary disease.
The findings, published in The Lancet Regional Health – Europe, suggest that female chronic obstructive pulmonary disease (COPD) patients with sleep apnea face an elevated lung cancer risk, while male COPD patients with sleep apnea appear to have a lower risk.
The study analyzed data from 62,903 COPD patients aged 55 and older, tracking health outcomes between 2017 and 2022. Of these, 4.6% (n = 2,898) developed lung cancer. Sleep apnea was associated with a significantly increased lung cancer risk in female COPD patients, with a cumulative incidence of 1,545 vs 1,350 per 100,000 person-years and an adjusted hazard ratio (aHR) of 1.31 (95% CI: 1.05–1.63). In contrast, male COPD patients with sleep apnea had a lower lung cancer risk, with a cumulative incidence of 1,632 vs 2,305 per 100,000 person-years and an aHR of 0.82 (95% CI: 0.70–0.95).
The risk was particularly pronounced in female COPD patients with hypoxia-related comorbidities, including emphysema (aHR: 2.65, 95% CI: 1.11–6.34), anemia (aHR: 2.09, 95% CI: 1.25–3.48), and cerebrovascular disease (aHR: 2.01, 95% CI: 1.17–3.45).
"The impact of sleep apnea on lung cancer might have sex-specific underlying mechanisms that require sex-specific management," said Kristiaan Proesmans from the Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University.
Prior research suggests that females with sleep apnea experience greater systemic inflammation for a given apnea-hypopnoea index than males, which may contribute to the increased cancer risk. Additionally, intermittent hypoxia, a hallmark of sleep apnea, has been linked to tumorigenesis, particularly in hypoxia-sensitive tissues.
The study also found that the protective effect of sleep apnea in male COPD patients disappeared in those using CPAP therapy (aHR: 0.83, 95% CI: 0.66–1.04) or oxygen supplementation (aHR: 0.99, 95% CI: 0.73–1.36), suggesting that the observed benefit may be limited to milder cases.
These findings highlight the need for a sex-specific approach to managing COPD patients with coexisting sleep apnea. The study underscores the potential role of intermittent hypoxia and systemic inflammation in cancer risk, warranting further investigation into personalized prevention strategies.
As an observational study based on insurance and hospital records, the analysis could not establish causality. Additionally, sleep apnea is often underdiagnosed, particularly in women, due to differences in clinical presentation, which may lead to an underestimation of risk, especially in the female COPD population. Further research is needed to explore the mechanisms underlying these sex differences and assess whether targeted interventions could mitigate the increased lung cancer risk in female COPD patients with sleep apnea.
The authors reported no conflicts of interest.
