Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer.
BACKGROUND
Circulating total cholesterol has been inversely associated with cancer risk; however, the role of reverse causation and the associations for high-density lipoprotein (HDL) cholesterol have not been fully characterized. We examined the relationship between serum total and HDL cholesterol and risk of overall and site-specific cancers among 29,093 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort.


METHODS
Fasting serum total and HDL cholesterol were assayed at baseline, and 7,545 incident cancers were identified during up to 18 years of follow-up. Multivariable proportional hazards models were conducted to estimate relative risks (RR).


RESULTS
Higher serum total cholesterol concentration was associated with decreased risk of cancer overall (RR for comparing high versus low quintile, 0.85; 95% confidence interval, 0.79-0.91; P trend <0.001; >276.7 versus <203.9 mg/dL), and the inverse association was particularly evident for cancers of the lung and liver. These associations were no longer significant, however, when cases diagnosed during the first 9 years of follow-up were excluded. Greater HDL cholesterol was also associated with decreased risk of cancer (RR for high versus low quintile, 0.89; 95% confidence interval, 0.83-0.97; P trend = 0.01; >55.3 versus <36.2 mg/dL). The inverse association of HDL cholesterol was evident for cancers of lung, prostate, liver, and the hematopoietic system, and the associations of HDL cholesterol with liver and lung cancers remained after excluding cases diagnosed within 12 years of study entry.


CONCLUSIONS
Our findings suggest that prior observations regarding serum total cholesterol and cancer are largely explained by reverse causation. Although chance and reverse causation may explain some of the inverse HDL associations, we cannot rule out some etiologic role for this lipid fraction.
Ahn
Jiyoung
J
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Lim
Unhee
U
Weinstein
Stephanie J
SJ
Schatzkin
Arthur
A
Hayes
Richard B
RB
Virtamo
Jarmo
J
Albanes
Demetrius
D
D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
D008076:Cholesterol, HDL; D002784:Cholesterol