Dataset Information

Polymorphisms of mismatch repair gene hMLH1 and hMSH2 and risk of gastric cancer in a Chinese population.

ABSTRACT: The purpose of this study was to determine the genotype and allele frequencies of hMLH1 (-93G>A and I219V) and hMSH2 (-118T>C and IVS12-6T>C) polymorphisms in patients with gastric carcinoma and normal controls, and to evaluate the association between these polymorphisms and the risk of gastric cancer in a hospital-based Chinese population. Genomic DNA was extracted from peripheral blood lymphocytes. A TaqMan assay was used to determine the genotype and allele frequencies of hMLH1 and hMSH2 polymorphisms in data obtained from 554 gastric cancer cases and 592 controls. Unconditional logistic regression was used to assess the association between the four single nucleotide polymorphisms (SNPs) and gastric carcinoma risk. No evidence of an association among any of the four polymorphisms and the risk of gastric cancer was observed. However, when gastric cancer patients were further stratified by age, gender, smoking status, alcohol use and clinicopathological characteristics, and compared with the control populations, the combined variant genotype hMSH2 -118T>C (TC+CC) was not only associated with an increased risk of gastric cancer in subgroups of younger subjects [ages ?63years; adjusted odds ratio (OR)=1.51, 95% confidence interval (CI), 1.05-2.16], but also with diffuse tumors (adjusted OR=1.41, 95% CI, 1.01-1.96). These data indicate that the polymorphisms of -93G>A, I219V and IVS12-6T>C are not associated with the risk of gastric cancer. However, hMSH2-118T>C combined with variant genotypes (TC+CC) may confer a potential risk of gastric cancer in the Chinese population.

SUBMITTER: Xiao XQ

PROVIDER: S-EPMC3362438 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Polymorphisms of mismatch repair gene hMLH1 and hMSH2 and risk of gastric cancer in a Chinese population.

Xiao Xian-Qiu XQ Gong Wei-DA WD Wang Shi-Zhi SZ Zhang Zheng-Dong ZD Rui Xiao-Ping XP Wu Guo-Zhong GZ Ren Feng F

Oncology letters 20111206 3

The purpose of this study was to determine the genotype and allele frequencies of hMLH1 (-93G>A and I219V) and hMSH2 (-118T>C and IVS12-6T>C) polymorphisms in patients with gastric carcinoma and normal controls, and to evaluate the association between these polymorphisms and the risk of gastric cancer in a hospital-based Chinese population. Genomic DNA was extracted from peripheral blood lymphocytes. A TaqMan assay was used to determine the genotype and allele frequencies of hMLH1 and hMSH2 poly ...[more]

PMID: 22740958

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Project description:PurposeOne major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of platinum resistance in EOC. The purpose of this study is to discover potential aberrant DNA methylation that contributes to drug resistance.MethodsBy initially screening of 16 platinum-sensitive/resistant samples from EOC patients with reduced representation bisulfite sequencing (RRBS), the upstream region of the hMSH2 gene was discovered hypermethylated in the platinum-resistant group. The effect of hMSH2 methylation on the cellular response to cisplatin was explored by demethylation and knockdown assays in ovarian cancer cell line A2780. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was employed to examine the methylation levels of hMSH2 upstream region in additional 40 EOC patient samples. RT-qPCR and IHC assay was used to detect the hMSH2 mRNA and protein expression in extended 150 patients.ResultsRRBS assay discovered an upstream region from - 1193 to - 1125 of hMSH2 was significant hypermethylated in resistant EOC patients (P = 1.06 × 10-14). In vitro analysis demonstrated that global demethylation increased cisplatin sensitivity along with a higher expression of the hMSH2 mRNA and protein. Knockdown hMSH2 reduced the cell sensitivity to cisplatin. MALDI-TOF mass spectrometry assay validated the strong association of hypermethylation of hMSH2 upstream region with platinum resistance. Spearman's correlation analysis revealed a significantly negative connection between methylation level of hMSH2 upstream region and its expression. The Kaplan-Meier analyses showed the high methylation of hMSH2 promoter region, and its low expressions are associated with worse survival. In multivariable models, hMSH2 low expression was an independent factor predicting poor outcome (P = 0.03, HR = 1.91, 95%CI = 1.85-2.31).ConclusionThe hypermethylation of hMSH2 upstream region is associated with platinum resistant in EOC, and low expression of hMSH2 may be an index for the poor prognosis.

Dataset Information

Polymorphisms of mismatch repair gene hMLH1 and hMSH2 and risk of gastric cancer in a Chinese population.

Publications

Polymorphisms of mismatch repair gene hMLH1 and hMSH2 and risk of gastric cancer in a Chinese population.

Similar Datasets

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