Discrepant Effect of High-Density Lipoprotein Cholesterol on the Hematologic Malignancy Risk: A Nationwide Cohort Study.

Objective: Although high-density lipoprotein cholesterol (HDL-C) is inversely associated with hematologic malignancies, modification by smoking has not been reported. We investigated how smoking and menopausal status modify these association. Methods: This population-based cohort study enrolled cancer-free individuals who underwent a national cancer screening in 2010 and followed up until December 2017. HDL-C levels were classified into eight groups based on 10 mg/dL intervals: (<30, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, or ≥90 mg/dL). Results: Among 4,517,892 participants, 5887 had lymphoma, 3348 had leukemia, and 12151 had unspecified hematologic malignancies. The adjusted hazard ratios (aHRs) for the lowest HDL-C levels compared to the 70-79 mg/dL range were 1.83 (1.45-2.31) for lymphoma, 3.14 (2.41-4.08) for leukemia, and 2.34 (2.01-2.72) for unspecified hematologic malignancy. The effects of low HDL-C levels on hematologic malignancies were similar in both men and women. Low HDL-C levels were associated with a higher risk of leukemia regardless of smoking status, but extremely high HDL-C levels were linked to a higher risk of leukemia (aHR, 2.32; 95% confidence interval [95% CI], 1.18-4.55) only in current smokers.The hazardous effect of low HDL-C levels on lymphoma was significant only in never smokers (aHR, 2.01; 95% CI, 1.51-2.68). Hazardous effects of low HDL-C levels on leukemia were observed only in post-menopausal women (aHR, 2.94; 95% CI, 1.69-5.11). Conclusion: Low HDL-C levels were associated with a higher risk of leukemia and lymphoma, with discrepancies based on smoking and menopausal status.