Site-specific Analysis of Total Serum Cholesterol and Incident Cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study¹

We studied the relation of total serum cholesterol to all cancer and site-specific cancer incidence in a cohort based on a probability sample of the United States population. A total of 5125 men (yielding 459 cancers) and 7363 women (398 cancers) were initially examined in 1971–75 and followed a median of 10 yr. An examination of age-adjusted incidence rates by cholesterol level showed an inverse association between cholesterol and all cancer; lung, colorectal, pancreatic, and bladder cancers; and leukemia. In women a weak inverse relation (reflecting an elevated rate among those only in the lowest cholesterol quintile) was apparent for all cancer; more prominent inverse associations were seen for cancers of the lung, pancreas, bladder, cervix, and for leukemia. A more detailed analysis of cholesterol and colorectal cancer revealed little association in both men and women. For an aggregate group of smoking-related cancers, the inverse relation was especially prominent: the multivariate relative risk estimates for subjects in the lowest cholesterol quintile, compared to those in the highest quintile, were 2.1 (1.1–3.8) and 3.3 (1.4–7.8) for men and women, respectively. The inverse association was present for smoking-related cancers diagnosed 6 or more yr after cholesterol determination in both men and women, suggesting that this association cannot be simply dismissed as a preclinical cancer effect. Further investigation of the cholesterol-cancer question, particularly the relation between cholesterol and smoking-related cancers, may provide useful etiological leads.