Introduction The relationship between serum cholesterol and cancer risk remains controversial. We examined the association between total serum cholesterol 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=39 004) for a mean follow-up of 11.7 years. We used Cox regression models with age as the underlying time metric to calculate HRs and their 95% CIs for 1 mmol/l increment of total cholesterol levels adjusting for age at first measurement, body mass index and smoking. Additionally, we performed lag time analyses and corrected HRs for regression dilution bias.

Results Significant relationships of cholesterol with cancer incidence were all inverse including liver cancer (HR=0.62; 95% CI 0.42 to 0.90) in males and cancers of the liver (0.62; 0.49 to 0.78), gallbladder (0.62; 0.44 to 0.85), breast (0.90; 0.85 to 0.94), and cancers of the lymph and haematopoietic tissue (0.85; 0.76 to 0.93) in females. In lag analyses excluding cancer events occurring up to 5 years after cholesterol measurements, relationships persisted for liver, gallbladder and breast cancer.

Conclusions Total cholesterol was negatively associated with cancer risk at several sites. Lag time analyses suggested that these associations are only partially explained by reverse causation.