Obstructive sleep apnea syndrome and causal relationship with female breast cancer: a mendelian randomization study

Although observational studies have reported a positive association between obstructive sleep apnea syndrome (OSAS) and breast cancer (BC) risk, causality remains inconclusive. We aim to explore whether OSAS is associated with etiology of BC by conducting a two-sample Mendelian randomization (MR) study in a Chinese population and Asian population from the Breast Cancer Association Consortium (BCAC). We found a detrimental causal effect of OSAS on BC risk in the primary analysis of our samples (IVW OR, 2.47 for BC risk per log-odds increment in OSAS risk, 95% CI = 1.86-3.27; P = 3.6×10^-10). This was very similar to results of the direct observational case-control study between OSAS and BC risk (OR = 2.80; 95% CI = 2.24-3.50; P =1.4×10^-19). Replication in the Asian population of the BCAC study also supported our results (IVW OR, 1.33 for BC risk per log-odds increment in OSAS risk, 95% CI = 1.13-1.56; P = 0.0006). Sensitivity analyses confirmed the robustness of our findings. We provide novel evidence that genetically determined higher risk of OSAS has a causal effect on higher risk of BC. Further studies focused on the mechanisms of the relationship between OSAS and breast carcinogenesis are needed.