Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12

Abstract

Serum folate concentration is inversely associated with the risk of cervical cancer, and the MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status.

Methylenetetrahydrofolate Reductase C677T Distribution among Cervical Cancer Patients at Dr. Hasan Sadikin General Hospital

“…The C677T MTHFR may have two contradictive effects in cervical cancer development. Reduced activity of the enzyme encoded by the SNP was assumed to have protective effect due to increased level of the enzyme substrate, 5,10-methylenetetrahydrofolate, which is 18 The hypermethylation of tumor suppresor genes, which represses its expression and favors tumor growth, is found in cervical cancer cells. Abnormal methylation process may also disrupt defense mechanism occured during integration process of virus gene to host genome.…”

Methylenetetrahydrofolate Reductase C677T Polymorphism and Cervical Cancer Risk: a Meta-Analysis

“…This common polymorphism of the MTHFR gene can lead to abnormal DNA methylation and DNA synthesis, possibly leading to an altered risk for cervical cancer. For almost a decade, many case-control studies investigating the association between MTHFR C677T polymorphism and cervical cancer risk have been published, but this association is still controversial (Sull et al, 2004;Kang et al, 2005;Zoodsma et al, 2005;Delgado-Enciso et al, 2006;Shekari et al, 2008;Kohaar et al, 2010;Mostowska et al, 2011;Prasad and Wilkhoo, 2011;Tong et al, 2011;von Keyserling et al, 2011). Thus, to establish a comprehensive picture of the relationship between MTHFR C677T polymorphism and cervical cancer risk, we performed this meta-analysis, and it is the first meta-analysis to investigate the association between MTHFR C677T polymorphism and cervical cancer risk up to now.…”

“…After discarding those which clearly did not meet the criteria, 19 studies were further assessed for eligibility (Piyathilake et al, 2000;Goodman et al, 2001;Gerhard et al, 2003;Lambropoulos et al, 2003;Sull et al, 2004;Kang et al, 2005;Zoodsma et al, 2005;Delgado-Enciso et al, 2006;Rao et al, 2006;Piyathilake et al, 2007;Nandan et al, 2008;Shekari et al, 2008;Agodi et al, 2010;Kohaar et al, 2010;Tong et al, 2010;Mostowska et al, 2011;Prasad and Wilkhoo, 2011;Tong et al, 2011;von Keyserling et al, 2011). After reviewing each original paper and extracting data, nine studies were excluded including five studies focusing on cervical intraepithelial neoplasia (Piyathilake et al, 2000;Goodman et al, 2001;Lambropoulos et al, 2003;Piyathilake et al, 2007;Agodi et al, 2010), three studies for not specifying genotypic frequencies of CC, CT, and TT (Gerhard et al, 2003;Nandan et al, 2008;Rao et al, 2006) and one study for overlapping data (Tong et al, 2010).…”

“…After reviewing each original paper and extracting data, nine studies were excluded including five studies focusing on cervical intraepithelial neoplasia (Piyathilake et al, 2000;Goodman et al, 2001;Lambropoulos et al, 2003;Piyathilake et al, 2007;Agodi et al, 2010), three studies for not specifying genotypic frequencies of CC, CT, and TT (Gerhard et al, 2003;Nandan et al, 2008;Rao et al, 2006) and one study for overlapping data (Tong et al, 2010). Finally, 10 casecontrol studies with a total of 2113 cervical cancer cases and 2804 controls were included into this meta-analysis (Sull et al, 2004;Kang et al, 2005;Zoodsma et al, 2005;Delgado-Enciso et al, 2006;Shekari et al, 2008;Kohaar et al, 2010;Mostowska et al, 2011;Prasad and Wilkhoo, 2011;Tong et al, 2011;von Keyserling et al, 2011). The detailed characteristics of these studies are summarized in Table 1.…”

“…Recent studies have shown that the MTHFR 677 TT genotype is associated with an increased risk of cancer risk, suggesting an important role of folate levels and subsequent impaired chromosomal DNA synthesis and aberrant DNA methylation in carcinogenesis (Dong et al, 2008;Zhang et al, 2010). There are also many published studies investigating the association between C677T polymorphism and cervical cancer risk, but the effect of MTHFR C677T polymorphism on cervical cancer risk remains controversial (Shekari et al, 2008;Kohaar et al, 2010;Mostowska et al, 2011;Prasad and Wilkhoo, 2011;Tong et al, 2011;von Keyserling et al, 2011). With the present meta-analyses, we aimed to assess the overall effect of the MTHFR C677T polymorphism on cervical cancer by including all available published papers.…”