Abstract 107: Pre-diagnostic levels of serum one-carbon metabolism biomarkers and risk of hepatocellular carcinoma.

Abstract

Abstract Pre-diagnostic levels of serum one-carbon metabolism biomarkers and risk of hepatocellular carcinoma BACKGROUND. It is well established that rats fed diets deficient in choline and methionine spontaneously develop hepatocellular carcinoma (HCC). Tumor DNA from these animals show a characteristic hypomethylation pattern, suggesting that disruption of the one-carbon metabolism (1CM) pathway may be an underlying mechanism for hepatocarcinogenesis. Prospective epidemiological data on circulating levels of 1CM biomarkers in relation to HCC risk have been lacking. METHODS. We prospectively examined the association between prediagnostic serum concentrations of betain, choline, cystathionine, homocysteine (Hcy), methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and risk of developing HCC among 297 incident HCC cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Conditional logistic regression method was used to calculate odds ratios (OR) and 95% confidence intervals (CI) adjusted for smoking, alcohol use, hepatitis B surface antigen (HBsAg) seropositivity and chronic liver disease. RESULTS. Higher serum levels of PLP were associated with statistically significantly reduced risk of HCC. The ORs (95% CIs) for the 2nd, 3rd, and 4th quartiles of serum PLP were 0.52 (0.32, 0.85), 0.57 (0.35, 0.93) and 0.35 (0.20, 0.60), respectively, compared with the 1st quartile (Ptrend<0.01). Among men with positive HBsAg, doubling serum choline concentration was associated with a statistically significant 58% decrease in HCC risk (OR=0.42; 95% CI: 0.19, 0.92) and doubling serum methionine concentration was positively associated with HCC risk (OR=2.94; 95% CI: 1.27, 6.82). Serum levels of cystathionine were associated with increased risk of HCC among all subjects (OR=1.92; 95% CI: 1.14, 3.21; Ptrend=0.01, comparing the 4th to 1st quartile). There was no association for HCC risk with circulating levels of 5-MTHF, Hcy, SAM, or SAH. CONCLUSION. Choline and PLP may be protective against the development of HCC whereas circulating methionine may be a risk factor for developing HCC, especially among high-risk individuals. Future investigation is warranted to test whether diets high in vitamin B6 are effective in preventing HCC development in high-risk populations. Citation Format: Lesley M. Butler, Renwei Wang, Teodoro Bottiglieri, Yu-Tang Gao, Jian-Min Yuan. Pre-diagnostic levels of serum one-carbon metabolism biomarkers and risk of hepatocellular 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 107. doi:10.1158/1538-7445.AM2013-107