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Investigation of methylenetetrahydrofolate reductase tagging polymorphisms with colorectal cancer in Chinese Han population.

ABSTRACT: The aim of this case-control study was to assess the relationship between the tagging polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene and the susceptibility to colorectal cancer (CRC) in a Chinese Han population. A custom-by-design 48-Plex SNPscan Kit was used to determine the genotypes of MTHFR rs3753584 T>C, rs9651118 T>C, rs1801133 G>A, rs4846048 A>G and rs4845882 G>A polymorphisms in 387 CRC patients and 1,536 non-cancer controls. The results revealed that MTHFR rs1801133 G>A polymorphism was associated with a decreased risk of overall CRC. While MTHFR rs4845882 G>A polymorphism conferred an increased risk to overall CRC. In a stratified analysis by CRC region, we found MTHFR rs3753584 T>C and rs9651118 T>C polymorphisms were associated with the increased risk of colon cancer. In addition, a significantly increased risk of rectum cancer associated with MTHFR rs3753584 T>C polymorphism was overt. However, MTHFR rs1801133 G>A polymorphism conferred a decreased risk to colon cancer. In conclusion, findings of the present study reveal that the tagging polymorphisms in MTHFR gene (rs3753584 T>C, rs9651118 T>C and rs4845882 G>A) are associated with the increased risk of CRC. However, MTHFR rs1801133 G>A polymorphism confers a decreased risk to CRC. Additional studies with larger sample size are needed to confirm these findings.

SUBMITTER: Zhang S

PROVIDER: S-EPMC5609940 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Investigation of methylenetetrahydrofolate reductase tagging polymorphisms with colorectal cancer in Chinese Han population.

Zhang Sheng S Chen Shuchen S Chen Yu Y Kang Mingqiang M Liu Chao C Qiu Hao H Wang Yafeng Y Tang Weifeng W

Oncotarget 20170629 38

The aim of this case-control study was to assess the relationship between the tagging polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene and the susceptibility to colorectal cancer (CRC) in a Chinese Han population. A custom-by-design 48-Plex SNPscan Kit was used to determine the genotypes of MTHFR rs3753584 T>C, rs9651118 T>C, rs1801133 G>A, rs4846048 A>G and rs4845882 G>A polymorphisms in 387 CRC patients and 1,536 non-cancer controls. The results revealed t ...[more]

PMID: 28969008

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Project description:What is already known about this subject* Numerous clinical studies, including a few prospective ones, have reported conflicting results on the impact of gene polymorphisms related to fluorouracil (FU) and oxaliplatin pharmacodynamics.What this study adds* This prospective study is the first to report that clinical response to FOLFOX is significantly related to methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (677C-->T and 1298A-->C), with a response rate of 37, 53, 63 and 80% in patients harbouring no, one, two or three favourable MTHFR alleles, respectively. * Only polymorphisms of genes related to oxaliplatin pharmacodynamics (GSTpi 105Ile-->Val and XPD 751Ly-->Gln) influenced progression-free survival. * These results corroborate the observation that response was related to the cumulative FU dose, whereas progression-free survival was related to the cumulative oxaliplatin dose.AimsTo test prospectively the predictive value of germinal gene polymorphisms related to fluorouracil (FU) and oxaliplatin (Oxa) pharmacodynamics on toxicity and responsiveness of colorectal cancer (CRC) patients receiving FOLFOX therapy.MethodsAdvanced CRC patients (n= 117) receiving FOLFOX 7 therapy were enrolled. Gene polymorphisms relevant for FU [thymidylate synthase (TYMS, 28 bp repeats including the G-->C mutation + 6 bp deletion in 3'UTR), methylenetetrahydrofolate reductase (MTHFR, 677C-->T, 1298A-->C), dihydropyrimidine deshydrogenase (IVS14+1G-->A) and Oxa: glutathione S-transferase (GST) pi (105Ile-->Val, 114Ala-->Val), excision repair cross-complementing group 1 (ERCC1) (118AAT-->AAC), ERCC2 (XPD, 751Lys-->Gln) and XRCC1 (399Arg-->Gln)] were determined (blood mononuclear cells).ResultsNone of the genotypes was predictive of toxicity. Response rate (54.7% complete response + partial response) was related to FU pharmacogenetics, with both 677C-->T (P= 0.042) and 1298A-->C (P= 0.004) MTHFR genotypes linked to clinical response. Importantly, the score of favourable MTHFR alleles (677T and 1298C) was positively linked to response, with response rates of 37.1, 53.3, 62.5 and 80.0% in patients bearing no, one, two or three favourable alleles, respectively (P= 0.040). Polymorphisms of genes related to Oxa pharmacodynamics showed an influence on progression-free survival, with a better outcome in patients bearing GSTpi 105 Val/Val genotype or XPD 751Lys-containing genotype (P= 0.054).ConclusionsThese results show that response to FOLFOX therapy in CRC patients may be driven by MTHFR germinal polymorphisms.

Dataset Information

Investigation of methylenetetrahydrofolate reductase tagging polymorphisms with colorectal cancer in Chinese Han population.

Publications

Investigation of <i>methylenetetrahydrofolate reductase</i> tagging polymorphisms with colorectal cancer in Chinese Han population.

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