Abstract 114: Circulating biomarkers of the one-carbon metabolism and renal cell carcinoma.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Circulating biomarkers of the one-carbon metabolism and renal cell carcinoma Mattias Johansson, Anouar Fanidi, Heiner Boeing, and Paul Brennan for the EPIC study group Abstract Context: The etiology of renal cell carcinoma (RCC) is not well understood but may involve dietary factors such as B-vitamins and further factors of the one-carbon metabolism (OCM) pathway. The objective of the current study was to investigate if variations in circulating biomarkers of one-carbon metabolism constitute differences in RCC risk. Design, Setting, and Participants: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries betweeen 1992 and 2000, of whom 385,747 donated a blood sample. The current study included 557 diagnosed RCC cases and 557 controls individually matched by country, sex, date of birth, and date of blood collection, as well as 840 additional unmatched controls (control group 2). Circulating concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic plasma samples and assessed in relation to RCC risk by logistic regression models while adjusting for relevant risk factors. Results: Study participants with increasing plasma levels of vitamin B6 had a lower risk of RCC in a clear dose response fashion (P for trend 4x10−6), the odds ratio when comparing the 2nd and 1st quartiles (OR2vs.1) being 0.65 (95% confidence interval [95% CI]: 0.47-0.90), OR3vs.1 being 0.55 (95% CI: 0.40-0.78), and OR4vs.1 being 0.39 (95% CI: 0.27-0.57). Plasma levels of the other investigated OCM factors did not display any clear association with RCC risk in overall conditional analysis (P for trend > 0.08). When comparing RCC cases with control group 2 we observed a similar decreasing risk with increasing levels of vitamin B6 (OR4vs.1: 0.45, 95% CI: 0.32-0.62, P for trend 4x10−6), and when combining all controls the P for trend was 2x10−7. We subsequently adjusted for known and potential risk factors, including hypertension, waist-to-hip ratio, educational attainment, smoking status, plasma cotinine, alcohol intake at recruitment, and body mass index, and the quartile specific OR estimates were similar in adjusted analysis (OR4vs.1: 0.51, 95% CI: 0.27-0.57, P for trend 5x10−4) and in unadjusted analysis restricted to subjects with complete covariate information (OR4vs.1: 0.46, 95% CI: 0.33-0.58, P for trend 1x10−5). Conclusion: Study participants with increasing circulating levels of vitamin B6 had lower risk of developing subsequent renal cell carcinoma within the EPIC study. Citation Format: Mattias Johansson, Anouar Fanidi, Heiner Boeing, Paul J. Brennan. Circulating biomarkers of the one-carbon metabolism and renal cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 114. doi:10.1158/1538-7445.AM2013-114