Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

Mu, Lina; Cao, Wei; Zhang, Zuo‐Feng; Cai, Lin; Jiang, Qingwu; You, Nai-Chieh Y.; Goldstein, Binh Y.; Wei, Guorong; Chen, Chuanwei; Lu, Qing-Yi; Zhou, Xin‐Da; Ding, Boxiao; Chang, Joon-Hyuk; Yu, Shun‐Zhang

doi:10.1007/s10552-007-9012-x

Cited by 44 publications

(29 citation statements)

References 32 publications

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“…However, in some groups of Northern Chinese [42,43], the 677T allele was more common than the 677C allele. In this study, the frequency of the 677T allele was most frequent in Chinese (27.5%), which was lower than the frequencies in other Chinese populations (30.7 to 44.6%) reported before [44][45][46][47][48]. In Singaporean Indians, the frequency of the 677T allele was 12.2%, being similar to the frequencies in Asian Indians living in South Africa (11%) [39] and UK (15.0%) [40], and to the frequency in Malays (10.6%) of this study.…”

Section: Discussioncontrasting

confidence: 83%

The Allele Frequencies of Three Polymorphisms in Genes Involved in Homocysteine Metabolism in a Group of Unrelated Healthy Singaporeans

Chen

2010

Disease Markers

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Abstract. The cystathionine β-synthase (CBS) 844ins68 polymorphism, methionine synthase (MS) A2756G SNP, and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T SNP are associated with homocysteine (Hcy) level in humans. Elevated Hcy level is considered a risk factor for atherosclerotic diseases among Asian populations. Therefore, the three polymorphisms may vary the risk for developing such diseases in Singaporeans. In this study, the three polymorphisms were determined in a group of unrelated healthy Singaporeans (273 Chinese, 127 Indians, and 156 Malays). Regarding allele frequencies, Indians had the highest frequencies of the CBS insertion allele (2.0%) and the MS 2756G allele (26.4%), while Chinese had the highest MTHFR 677T allele frequency (27.5%). In addition, the MTHFR 677T allele was found significantly lower in Chinese males than in their female counterparts. As the CBS insertion allele was suggested to be associated with lower Hcy level, whereas the MS 2756G allele and the MTHFR T/T genotype were related to higher Hcy level, the MS A/G or G/G genotype and the MTHFR T/T genotype were considered double genetic risk factors for elevated Hcy level. The frequency of such double genetic risk was 0.7% (4 subjects) in the total population consisting of 3 Chinese (1.1%) and 1 Malays (0.6%). No MTHFR T/T genotype was found in Indians. Such results suggested that Chinese could have higher Hcy levels than Malays while the situation for Indians was complicated. Since human Hcy levels are also affected by environmental factors, further studies are required to better evaluate the association between these three polymorphisms and Hcy levels and/or disease susceptibilities in Singaporeans.

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Section: Discussioncontrasting

confidence: 83%

The Allele Frequencies of Three Polymorphisms in Genes Involved in Homocysteine Metabolism in a Group of Unrelated Healthy Singaporeans

Chen

2010

Disease Markers

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“…The results in the present study are different in some ways from those observed in 2 previous studies, performed one in an European population (Saffroy et al, 2004) and another in a Chinese population (Mu et al, 2007). In the former, an association was detected between the MTHFR SNP and the occurrence of HCC only in patients with end stage liver disease of alcoholic origin, but not in patients with HCC arisen in cirrhosis of viral origin or in noncirrhotic livers.…”

Section: Discussioncontrasting

confidence: 99%

“…Not surprisingly, therefore, the relationship between MTHFR C677T SNP and the occurrence of malignant diseases has been explored in leukemia (Franco et al, 2001;Robien and Ulrich, 2003;Skibola et al, 1999), stomach (Boccia et al, 2008), colon (Ma et al, 1997;Sharp and Little, 2004;Slattery et al, 1999), breast (Beilby et al, 2004), and bladder (Lin et al, 2004) cancer. Two studies in patients with HCC have yielded conflicting results (Mu et al, 2007;Saffroy et al, 2004).…”

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confidence: 99%

MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption

Fabris

Toniutto

Falleti

et al. 2008

Alcoholism Clin & Exp Res

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Background: A single nucleotide polymorphism (SNP) C677T in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified. The TT or CT genotypes show a marked reduction of the enzyme activity; this causes higher homocysteine levels and alterations of folate metabolism. Folate metabolism is essential for DNA synthesis and methylation, crucial steps in carcinogenesis. In this paper, we investigated whether the MTHFR C677T SNP could influence the occurrence of hepatocellular carcinoma (HCC) in a cohort of patients transplanted for end stage liver disease of different etiologies.Methods: Two hundred and twelve consecutive patients who underwent liver transplantation for end stage liver disease due to hepatitis B or C, alcoholic liver disease, and other causes were studied. Two hundred and thirty-six blood donors served as controls. Focal hepatic lesions were searched in the sectioned explanted livers. The presence of the MTHFR C677T SNP was determined via polymerase chain reaction amplification.Results: Among the 65 patients with HCC, 22 had the CC genotype, 30 the CT, and 13 the TT genotype. Only in patients with alcoholic liver disease was a significant association detected between the TT genotype and the presence of liver cancer (6 ⁄ 17 vs. 5 ⁄ 46, p < 0.05). At stepwise logistic regression analysis the independent selected predictors of HCC were found: age at transplantation >55 years (p < 0.001) and the association among male gender, alcoholic liver disease, and MTHFR TT genotype (p = 0.002).Conclusions: The present study suggests that male TT carriers with alcoholic cirrhosis bear an increased risk of developing HCC.

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“…Based on the inclusion criteria, five case-control studies from four publications were included in this meta-analysis (Mu et al, 2007;Yuan et al, 2007;Kwak et al, 2008;Cui et al, 2012) and 21 studies were excluded. The flow chart for the study selection is summarized in Figure 1.…”

Section: Characteristics Of the Studies Includedmentioning

confidence: 99%

Significant association between the MTHFR A1298C polymorphism and hepatocellular carcinoma risk: a meta-analysis

Chang¹,

Meng²,

Jh³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The A1298C polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene has been reported to be associated with hepatocellular carcinoma (HCC), but there are conflicting results from previous studies. The present study aimed to investigate the association between this polymorphism and the risk of HCC using a meta-analysis of the published studies. Published literature from PubMed and Embase databases was systematically searched to identify relevant studies before October 2014. The Begg test was used to measure publication bias. Sensitivity analyses were performed to ensure the authenticity of the outcome. The meta-analysis results showed significant association between the MTHFR A1298C polymorphism and HCC risk (CC vs AA: OR = 0.52, 95%CI = 0.33-0.81; CC vs AC: OR = 0.50, 95%CI = 0.32-0.79; dominant model: OR = 1.94, 95%CI = 1.24-3.02; recessive model: OR = 1.00, 95%CI = 0.84-1.18). In the subgroup analysis, significant associations 15973 MTHFR A1298C polymorphism and hepatocellular carcinoma risk ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 15972-15980 (2015) between the MTHFR A1298C polymorphism and HCC risk were found in Asians (CC vs AA: OR = 0.46, 95%CI = 0.27-0.78; CC vs AC: OR = 0.41, 95%CI = 0.24-0.71; dominant model: OR = 2.27, 95%CI = 1.33-3.86; recessive model: OR = 1.03, 95%CI = 0.86-1.24). Our results suggest that the MTHFR A1298C polymorphism might be related to increased risk of HCC in Asians. Further large and well-designed studies are needed to confirm these conclusions.

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Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

Cited by 44 publications

References 32 publications

The Allele Frequencies of Three Polymorphisms in Genes Involved in Homocysteine Metabolism in a Group of Unrelated Healthy Singaporeans

The Allele Frequencies of Three Polymorphisms in Genes Involved in Homocysteine Metabolism in a Group of Unrelated Healthy Singaporeans

MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption

Significant association between the MTHFR A1298C polymorphism and hepatocellular carcinoma risk: a meta-analysis

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