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Cancer Epidemiol Biomarkers Prev. 2013 Oct;22(10):1884-93. doi: 10.1158/1055-9965.EPI-13-0497. Epub 2013 Jul 29.

Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma.

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  • 1Authors' Affiliations: Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute; and Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; Institute of Metabolic Disease, Baylor Research Institute, Dallas, Texas; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; and Department of Epidemiology, Shanghai Cancer Institute, Shanghai, PR China.

Abstract

BACKGROUND:

Rats fed diets deficient in choline develop hepatocellular carcinoma. Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and hepatocellular carcinoma risk have been lacking.

METHODS:

We prospectively examined the association between prediagnostic serum concentrations of one-carbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing hepatocellular carcinoma based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate ORs and 95% confidence intervals (CI) adjusted for established risk factors for hepatocellular carcinoma.

RESULTS:

Serum choline and PLP were associated with statistically significant reduced risk of hepatocellular carcinoma, whereas serum cystathionine, methionine, and SAM were associated with increased hepatocellular carcinoma risk (all Ptrend < 0.05). The inverse associations for hepatocellular carcinoma risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16-0.78; P = 0.010) and 0.44 (0.25-0.78; P = 0.005), respectively. There were no associations for hepatocellular carcinoma risk with 5-MTHF, betaine, or homocysteine.

CONCLUSION:

The inverse associations between choline and vitamin B6 and the risk of hepatocellular carcinoma development are novel and warrant further investigation.

IMPACT:

Identifying new modifiable factors for hepatocellular carcinoma prevention is warranted.

[PubMed - indexed for MEDLINE]
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