J Lipid Atheroscler.  2025 Jan;14(1):94-105. 10.12997/jla.2025.14.1.94.

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

• Nam SY
• Jo J
• Lee WK

• KMID: 2565043
• DOI: http://doi.org/10.12997/jla.2025.14.1.94

Abstract

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.

Keyword

High density lipoprotein cholesterol; Lymphoma; Leukemia; Smoking; Menopause