Discrepant effect of high-density lipoprotein cholesterol on esophageal and gastric cancer risk in a nationwide cohort

Background: The relationship between high-density lipoprotein cholesterol (HDL-C) and gastroesophageal cancer is not constant. Methods: In this population-based cohort study, 4.518 million cancer-free individuals among those who underwent national cancer screening in 2010 were enrolled and followed up until December 2017. HDL-C level was classified into eight groups at 10 mg/dL intervals. The risk of gastroesophageal cancers by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results: During 8 years of follow-up, 38,362 gastric and 3022 esophageal cancers developed. Low HDL-C level was associated with an increased risk of gastric cancer; aHR was 1.19 (95% CI 1.09–1.30) for HDL-C < 30 mg/dL, 1.07 (95% CI 1.03–1.12) for HDL-C of 30–39 mg/dL, and 1.07 (95% CI 1.03–1.12) for HDL-C of 40–49 mg/dL comparing to HDL-C of 60–69 mg/dL. HDL-C was positively associated with esophageal cancer risk; aHR was 1.30 (1.12–1.51) for HDL-C of 70–79 mg/dL, 1.84 (1.53–2.22) for HDL-C of 80–89 mg/dL, 2.10 (1.67–2.61) for HDL-C ≥ 90 mg/dL. These site-specific effects of HDL-C were robust in sensitivity analyses. The range of HDL-C for the lowest cancer risk was different by sex and site. The hazardous effect of low HDL-C on gastric cancer was prominent in never and past smokers, and extremely high HDL-C increased gastric cancer risk (aHR 1.19; 95% CI 1.04–1.36) only in current smokers. Unfavorable effect of high HDL-C on gastroesophageal cancer risk was remarkable in smokers. Conclusions: Low HDL-C increased the risk of gastric cancer, wherein high HDL-C was associated with esophageal cancer risk with discrepancies by sex and smoking status.