Total Serum Cholesterol and Cancer Incidence in the Metabolic Syndrome and Cancer Project (Me-Can)

Objective: To investigate the association between total serum cholesterol (TSC) and cancer incidence in the Metabolic syndrome and Cancer project (Me-Can). Methods: Me-Can consists of seven cohorts from Norway, Austria, and Sweden including 289,273 male and 288,057 female participants prospectively followed up for cancer incidence (n = 38,978) with a mean follow-up of 11.7 years. Cox regression models with age as the underlying time metric were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) for quintiles of cholesterol levels and per 1 mmol/l, adjusting for age at first measurement, body mass index (BMI), and smoking status. Estimates were corrected for regression dilution bias. Furthermore, we performed lag time analyses, excluding different times of follow-up, in order to check for reverse causation. Results: In men, compared with the 1st quintile, TSC concentrations in the 5th quintile were borderline significantly associated with decreasing risk of total cancer (HR = 0.94; 95% CI: 0.88, 1.00). Significant inverse associations were observed for cancers of the liver/intrahepatic bile duct (HR = 0.14; 95% CI: 0.07, 0.29), pancreas cancer (HR = 0.52, 95% CI: 0.33, 0.81), non-melanoma of skin (HR = 0.67; 95% CI: 0.46, 0.95), and cancers of the lymph-/hematopoietic tissue (HR = 0.68, 95% CI: 0.54, 0.87). In women, hazard ratios for the 5th quintile were associated with decreasing risk of total cancer (HR = 0.86, 95% CI: 0.79, 0.93) and for cancers of the gallbladder (HR = 0.23, 95% CI: 0.08, 0.62), breast (HR = 0.70, 95% CI: 0.61, 0.81), melanoma of skin (HR = 0.61, 95% CI: 0.42, 0.88), and cancers of the lymph-/hematopoietic tissue (HR = 0.61, 95% CI: 0.44, 0.83). Conclusion: TSC was negatively associated with risk of cancer overall in females and risk of cancer at several sites in both males and females. In lag time analyses some associations persisted, suggesting that for these cancer sites reverse causation did not apply.