Dataset Information

A Meta-Analysis: Methylenetetrahydrofolate Reductase C677T Polymorphism in Gastric Cancer Patients Treated with 5-Fu Based Chemotherapy Predicts Serious Hematologic Toxicity but Not Prognosis.

ABSTRACT: 5-fluorouracil (5-Fu) metabolism associated enzyme, methylenetetrahydrofolate reductase (MTHFR)'s polymorphism C677T can affect enzyme activity and a series of studies have been performed to examine the association of this MTHFR polymorphism with the clinical outcomes of gastric cancer (GC) patients treated with 5-Fu based chemotherapies. However, the results are inconsistent and inconclusive. Therefore, a more comprehensive summary like meta-analysis on this topic is needed. We performed a systematic literature search of PubMed and Embase up to May 20, 2017. Researches exploring MTHFR polymorphisms C677T's relationship with the clinical outcomes (response rate, overall survival and toxicity) of GC patients treated with 5-Fu based chemotherapy were included. The association was measured by odds ratios (ORs) or hazard ratios (HRs) combined with their 95% confidence intervals (CIs) using random/fixed effects model according to the studies' heterogeneity. Subgroup, sensitivity and publication bias analyses were conducted. Thirteen studies were finally included in this meta-analysis. No significant association was found between response rate [TT/ (CC+CT) OR=1.31, 95% CI: 0.62-2.76] or overall survival [(CT+TT)/CC HR=1.05, 95% CI: 0.86-1.26; TT/(CT+CC) HR=1.48, 95% CI: 0.53-4.15] and MTHFR polymorphism C677T. However, GC patients with CC or CT genotype tended to experience less severe hematologic toxicity than those with TT genotype [(CC+CT)/TT OR=0.66, 95% CI: 0.48-0.91]. In conclusion, MTHFR C677T polymorphism predicts severe hematologic toxicity in GC patients receiving 5-Fu based chemotherapy, but not the efficiency.

SUBMITTER: Tang C

PROVIDER: S-EPMC5868173 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A Meta-Analysis: Methylenetetrahydrofolate Reductase C677T Polymorphism in Gastric Cancer Patients Treated with 5-Fu Based Chemotherapy Predicts Serious Hematologic Toxicity but Not Prognosis.

Tang Cheng C Yu Shan S Jiang Huiqin H Li Wei W Xu Xiaojing X Cheng Xi X Peng Ke K Chen Erbao E Cui Yuehong Y Liu Tianshu T

Journal of Cancer 20180228 6

5-fluorouracil (5-Fu) metabolism associated enzyme, methylenetetrahydrofolate reductase (MTHFR)'s polymorphism C677T can affect enzyme activity and a series of studies have been performed to examine the association of this MTHFR polymorphism with the clinical outcomes of gastric cancer (GC) patients treated with 5-Fu based chemotherapies. However, the results are inconsistent and inconclusive. Therefore, a more comprehensive summary like meta-analysis on this topic is needed. We performed a syst ...[more]

PMID: 29581785

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Project description:BackgroundMethylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate. The non-synonymous single nucleotide polymorphism (nsSNP), C677T (Ala>Val, rs1801133), has been verified to impair enzyme activity. The association with cancer susceptibility, including hepatocellular carcinoma (HCC), has also been widely studied. The results, however, were inconsistent. To shed light on the influence of MTHFR C677T polymorphism on HCC, a meta-analysis was conducted.MethodsThe meta-analysis of C677T consisted of 10 studies (1814 cases/2862 controls). The association was measured by using random-effect (RE) or fixed-effect (FE) odds ratio (OR) combined with 95% confidence intervals (CIs) according to the studies' heterogeneity.ResultsUsing genetic model analysis, C677T polymorphism was found to increase the risk of HCC in a complete overdominant model, which indicates that heterozygotes CT are at a lesser risk of HCC than either homozygotes CC or TT. Meta-analyses of the 10 studies showed that the TT genotype increased the risk of HCC as compared to the CT genotype: FE OR was 1.20 (95%CI: 1.00-1.45, p for heterogeneity = 0.21). When subgroup analysis was done between the HCC cases and the chronic liver disease (CLD) patients of four studies, meta-analysis showed that individuals with the TT genotype had increased HCC risk compared with those with the CT genotype: FE OR (TT vs. CT) reached 1.81 (1.22-2.71, p for heterogeneity = 0.25). Meanwhile, the C677T polymorphism also increased HCC risk in a recessive model when cases were compared to CLD patients of four studies: RE OR reached 1.85 (95%CI: 1.00-3.42, p for heterogeneity = 0.06). Overall, there was some extent heterogeneity when analyses were performed in various models. There was no publication bias.ConclusionMTHFR C677T polymorphism increased the risk of HCC in an overdominant model, and might be a risk factor for HCC occurrence, especially in CLD patients. The association warranted further studies.

Project description:BackgroundMethylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism is involved in DNA synthesis, DNA repair and DNA methylation. The functional polymorphism of MTHFR gene, C677T has been shown to impact various diseases and implicated as a risk factor for the development of various neurodegenerative disorders including glaucoma.MethodsWe investigated MTHFR C677T genotypes and alleles frequencies in primary glaucoma [primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG)] patients and matched healthy controls in a case-control study. Two hundred ten primary glaucoma cases were studied for MTHFR C677T polymorphism and compared with 280 controls taken from the healthy population, employing the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The MTHFR gene was amplified using specific primers. The PCR products (294 bp) was subsequently digested with HinfI (New England Biolabs) at 37 °C for 12 h, separated by electrophoresis on 2 % agarose gels, and visualized with ethidium bromide staining. The restriction digestion yielded 168 and 126 bp fragments for TT, 294, 168 and 126 bp fragments for CT and undigested PCR product 294 bp indicating CC genotype.ResultsWe found the frequency of the genotypes and alleles of MTHFR C677T differ significantly between cases and controls. The frequencies of allele T and genotype CT were significantly higher while the frequencies of allele C and genotype CC were lower in primary glaucoma patients as compared to controls (p <0.05). Upon stratification of our results into POAG and PACG, significantly higher frequencies of allele T (19.44 %) and genotype CT (38.89 %) were found in POAG patients compared to controls (12.5 % and 25 % respectively). The frequencies of alleles and genotypes were almost similar in PACG and controls (p = 0.8).ConclusionThis study indicates that the allele T and genotype CT of MTHFR C677T polymorphism are significantly associated with POAG while allele C and CC genotype may be protective for it. We conclude that the MTHFR C677T polymorphism increases the risk for POAG development in Saudi population and can be a genetic marker however, further studies are needed with multiple-ethnic populations affected with POAG to strengthen these findings.

Dataset Information

A Meta-Analysis: Methylenetetrahydrofolate Reductase C677T Polymorphism in Gastric Cancer Patients Treated with 5-Fu Based Chemotherapy Predicts Serious Hematologic Toxicity but Not Prognosis.

Publications

A Meta-Analysis: Methylenetetrahydrofolate Reductase C677T Polymorphism in Gastric Cancer Patients Treated with 5-Fu Based Chemotherapy Predicts Serious Hematologic Toxicity but Not Prognosis.

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