Abstract B124: A prospective study of one-carbon metabolism biomarkers and risk of renal cell carcinoma.

Abstract

Abstract B124 Background Folate and other one-carbon nutrients have been hypothesized to play a role in carcinogenesis. No studies have examined biomarkers for nutrients involved in one-carbon metabolism and risk of renal cell carcinoma (RCC). Methods We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a prospective study of Finnish male smokers aged 50-69 years. The Finnish population does not have mandatory folic acid fortification of the food supply. Prediagnostic folate, pyridoxal 5-phosphate (vitamin B6), vitamin B12, cysteine, riboflavin and homocysteine concentrations were measured in fasting serum from 224 incident RCC cases and 224 controls. Controls were alive and cancer-free at date of case diagnosis, and were matched to cases on age and date of baseline serum collection. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for smoking, body mass index, leisure physical activity, and dietary intake of fat, protein, methionine, and energy. Results Subjects with clinically deficient folate status (≤3ng/ml) had a significantly increased RCC risk compared to subjects with adequate status (>3 ng/ml) (OR=1.68, 95% CI 1.06-2.65). When analyzed in quartiles, serum folate also was inversely associated with RCC (highest vs. lowest quartile, OR=0.67, 95% CI 0.37-1.20, P-trend=0.19). The other one-carbon metabolism biomarkers were not associated with RCC risk. An analysis that included all biomarkers showed a non-significant reduced risk for the a priori expected lowest risk profile (above the median in all biomarkers and below the median for homocysteine) compared to all other subjects (OR=0.24, CI 0.05-1.13). Restricting the analysis to cases diagnosed after at least two years of follow-up did not appreciably change the risk estimates. Conclusions Our study in male smokers suggests that inadequate folate status may be associated with an increased risk of renal cell carcinoma. This suggestive association with RCC warrants further exploration in other epidemiologic studies that include women and non-smokers. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B124.