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Association study between genetic polymorphisms in folate metabolism and gastric cancer susceptibility in Chinese Han population: A case-control study.

ABSTRACT: BACKGROUND:Gastric cancer (GC), the second leading cause of cancer mortality behind lung cancer worldwide, is caused by both genetic and environmental factors. In this study, we evaluated the association between the genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTR), and methyltransferase reductase (MTRR) genes and ischemic stroke risk in Chinese population. METHODS:A case-control study was conducted including 681 patients with GC and 756 healthy controls. Chi-squared test/Fisher's exact test and genetic model were used to evaluate associations. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. RESULTS:In the allele model, using the chi-square test, we found that the rs1532268 in MTRR with a minor allele T was significantly associated with increased risk of GC (OR = 1.24, 95% CI, 1.00-1.53; p = 0.048). In the genetic model analysis, we identified that the single-nucleotide polymorphism of the rs1801133 in MTHFR could increase the GC risk in the recessive model (OR = 1.31, 95% CI, 1.01-1.70; p = 0.042) and log-additive model (OR = 1.19, 95% CI, 1.02-1.38; p = 0.025). In MTHFR, a strong linkage of rs2274976 and rs1801133 was detected. The haplotype "GC" in the MTHFR gene was found to prominently increase the risk of GC (OR = 1.26, 95% CI: 1.07-1.47; p = 0.005). Other haplotypes did not display the correlativity. CONCLUSION:This study suggested that MTR and MTHFR polymorphisms may contribute to increase the risk of GC.

SUBMITTER: Wei L

PROVIDER: S-EPMC6503009 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Association study between genetic polymorphisms in folate metabolism and gastric cancer susceptibility in Chinese Han population: A case-control study.

Wei Lusha L Niu Fanglin F Wu Jiamin J Chen Fulin F Yang Hua H Li Jing J Jin Tianbo T Wu Yifei Y

Molecular genetics & genomic medicine 20190318 5

<h4>Background</h4>Gastric cancer (GC), the second leading cause of cancer mortality behind lung cancer worldwide, is caused by both genetic and environmental factors. In this study, we evaluated the association between the genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTR), and methyltransferase reductase (MTRR) genes and ischemic stroke risk in Chinese population.<h4>Methods</h4>A case-control study was conducted including 681 patients wi ...[more]

PMID: 30884202

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Project description:BackgroundThe polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD1) has been reported as a risk factor for neural tube defects (NTDs). In the present study, we aimed to investigate whether the single-nucleotide polymorphisms (SNPs) of MTHFD1 gene are associated with NTDs in a Chinese population and to determine their mechanism of action.Material and methodsMTHFD1 gene was scanned in a total of 270 NTDs cases and 192 healthy controls by using next-generation sequencing (NGS) method. After quality control procedures, 208 selected SNP sites in MTHFD1 gene were enrolled for follow-up statistical association analyses. Functional analyses were also performed for significant SNPs through bioinformatics analysis. Folic acid levels of brain tissue in available NTDs cases and healthy controls (113 and 123, respectively) were measured. Statistical and bioinformatics analyses were performed to investigate the relationship between SNPs in MTHFD1 and susceptibility to NTDs.ResultsStatistical analysis showed that 2 independent SNPs, rs1956545 and rs56811449, confer the risk of NTDs (P value=0.0195, OR (odds ratio)=1.41, 95% CI (confidence interval)=1.06-1.88; P value=0.0107, OR=0.56, 95% CI=0.36-0.87). The haplotype GGGG, which consists of 4 SNPs (rs2236225, rs2236224, rs1256146, and rs6573559), is also associated with risk of NTDs (P value=0.0438, OR=0.7180, 95% CI=0.5214-0.9888). The risk allele C of rs1956545 is also associated with decreased folic acid levels in the brain (P value=0.0222, standard beta=-0.2238, 95% CI=-0.4128 - -0.0349) according to analysis in the subset of NTDs cases and healthy controls. Bioinformatics analysis indicates that rs1956545 and rs56811449 are within ENCODE regulatory regions, the open chromatin regions of blastula Trophoblast cell line, and histone-marked region of brain astrocyte cell line.ConclusionsThe polymorphism of SNP loci rs1956545 and rs56811449 as well as a haplotype in MTHFD1 gene could serve as an indicator for the occurrence of NTDs in Chinese population and some specific genotypes of the loci may have lower risk of developing NTDs.

Dataset Information

Association study between genetic polymorphisms in folate metabolism and gastric cancer susceptibility in Chinese Han population: A case-control study.

Publications

Association study between genetic polymorphisms in folate metabolism and gastric cancer susceptibility in Chinese Han population: A case-control study.

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