Abstract B102: Serum compounds involved in the one-carbon metabolism and urothelial cell carcinoma risk: A nested case-control study within EPIC

Abstract

Abstract Introduction: Folate is, in combination with vitamin B6, vitamin B12 and homocysteine, involved in one-carbon-metabolism affecting DNA synthesis and methylation which may play a role in carcinogenesis. This nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) is the first prospective study that investigated associations between prediagnostic serum folate, homocysteine, vitamin B6 and vitamin B12 and the risk of urothelial cell carcinomas (UCC). Methods: 847 UCC first incident cases were matched to 847 controls for gender, age at baseline, study center, date of blood collection, time of day of blood collection, and fasting status. Serum concentrations of folate and vitamin B12 were determined with an immuno-analyser. Serum vitamin B6 concentrations were measured by reverse-phase high-performance liquid chromatography (HPLC) and serum homocysteine concentrations by an enzyme cycling assay. Incidence rate ratios (IRR) were estimated with conditional logistic regression with detailed adjustment for smoking status, smoking duration and smoking intensity. All analyses were conducted for total UCC and for two prognostic subgroups of UCC, defined by tumor stage and grade. Ta grade 1 or 2 tumors were defined as non-aggressive (n=377) while all other grade and stage combinations were defined as aggressive (n=395). Results: A reduced risk of UCC was found for higher levels of serum folate (IRR highest vs. lowest quartile 0.73; 95%CI 0.52–1.01, p-trend=0.04), although this was apparent only for current smokers. Serum folate was inversely associated with aggressive UCC risk (IRR highest vs. lowest quartile 0.59; 95%CI 0.37–0.95, p-trend=0.04), but not with the risk of non-aggressive UCC. No associations were observed between serum homocysteine, vitamin B6 and B12 and UCC risk. Conclusion: This large European cohort study shows that high serum concentrations of folate may reduce the risk of UCC, in particular the risk of aggressive UCC. However, residual confounding by smoking can not be excluded. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B102.