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Genetic C677T polymorphisms of methylenetetrahydrofolate reductase and one‐carbon metabolites as prognostic predictors for survival outcome of patients with hepatocellular carcinoma.
Author(s) -
Kuo Chang Sheng,
Hwung ChyiYun,
Kuo ShineDou,
Cheng ChinPao,
Chen ChienHung,
Lu ChinLi,
Huang RweiFen
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1077.12
Subject(s) - methylenetetrahydrofolate reductase , medicine , hazard ratio , gastroenterology , hepatocellular carcinoma , vitamin b12 , proportional hazards model , thymidylate synthase , genotype , confidence interval , biology , cancer , genetics , gene , fluorouracil
The aims of this study were to investigate the association between methylene‐ tetrahydrofolate reductase(MTHFR) C677T polymorphism, two thymidylate synthase(TS) polymorphylisms (a tandem‐repeat of 5′UTR and 6‐bp ins/del polymophylism on the 3′UTR), one carbon‐status and survival rates of patients with hepatocellular carcinoma (HCC). The cohort study included 232 HCC patients. MTHFR C677T and TS polymorphisms were analyzed by real‐time PCR. Survival outcome of HCC patients was analyzed by Kaplan–Meier method and Cox proportional hazard model. The results showed that Cox elevated serum AFP (>;200 vs. <20, HR=3.61, CI=1.99–6.55), vitB12(>;1500 vs. <699, HR=2.69, CI =1.24–5.84), RBC folate (>;818 vs. <566, HR=2.05, CI=1.11–3.78), overweight (>;24 vs. <18.5, HR=4.86, CI=1.11–21.17) and increase tumor size (5~10 vs. <5, HR=1.97; CI=1.18–3.27) will elevate the hazard ratio of HCC death. MTHFR 677 CT or TT genotypes were associated with reduced hazard ratio of HCC death (CT/TT vs. CC, HR=0.48; CI=0.30–0.79). CC genotype in combination with high folate status (566–818 ng/mL) or with elevated vitamin B12 levels (699–1500 ng/ mL) were associated with increased HR (HR=2.02, 95%CI=1.00–4.11) for RBC; (HR=2.04, 95% CI=1.11–3.77) for vitamin B12. Taken together, folate, B12 and MTHFR C677T polymorphism serve as the potential predictors for survival outcome of HCC patients.