Baseline and on-treatment high-density lipoprotein cholesterol and the risk of cancer in randomized controlled trials of lipid-altering therapy.
OBJECTIVE
We sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions.


BACKGROUND
Epidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk.


METHODS
A systematic MEDLINE search identified lipid intervention RCTs with >or=1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm.


RESULTS
A total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001).


CONCLUSIONS
There is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking.
Jafri
Haseeb
H
Molecular Cardiology Research Institute, Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Alsheikh-Ali
Alawi A
AA
Karas
Richard H
RH
D000328:Adult; D017677:Age Distribution; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D017678:Sex Distribution; D016019:Survival Analysis
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents