Serum High-Density Lipoprotein Cholesterol and Risk of Non-Hodgkin Lymphoma

Lymphoma patients often exhibit abnormal lipid metabolism. Recent evidence, however, suggests that a decrease in circulating high-density lipoprotein cholesterol (HDL-C) may occur during lymphomagenesis, reflecting underlying etiology such as inflammation. We investigated the relationship between prediagnostic HDL-C and non-Hodgkin lymphoma (NHL) in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. At baseline, serum HDL-C and total cholesterol concentrations from fasting blood, information on diet and lifestyle, and direct measurements of height, weight, and blood pressure were obtained from 27,074 healthy male smokers of ages 50 to 69 years. Cox proportional hazards models with age as underlying time metric was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). We found no association between total or non-HDL cholesterol and the 201 incident NHL cases ascertained during the follow-up (1985-2002), but observed an inverse association between HDL-C and NHL, which changed with length of follow-up. High HDL-C was associated with lower risk of all NHL during the first 10 years (n = 148; RR for 5th versus 1st quintile, 0.35; 95% CI, 0.19-0.62; P(trend) < 0.0001), but not with diagnoses during later follow-up (n = 53; RR, 1.31; 95% CI, 0.55-3.10). The inverse association was similar for NHL subtypes and was not modified by obesity, blood pressure, physical activity, or alcohol intake, but seemed to be stronger in men with lower duration of smoking (P(interaction) = 0.06). Our findings implicate HDL-C as a preclinical indicator of NHL and warrant further prospective investigations for its etiologic contribution.