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Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy.

ABSTRACT: DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms of DNMT1 may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms of DNMT1 gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of the DNMT1 gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs of DNMT1 and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51-0.91, P = 0.007). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49-0.91, P = 0.010). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of the DNMT1 gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients.

SUBMITTER: Jia Z

PROVIDER: S-EPMC4819102 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy.

Jia Zhifang Z Wu Xing X Cao Donghui D Wang Chuan C You Lili L Jin Meishan M Wen Simin S Cao Xueyuan X Jiang Jing J

Disease markers 20160321

DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms of DNMT1 may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms of DNMT1 gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of the DNMT1 gene were genotyped by ...[more]

PMID: 27087738

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Project description:BackgroundAdjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC).MethodsThe analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS.ResultsWe found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC.ConclusionSNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.

Dataset Information

Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy.

Publications

Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy.

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