Polymorphism of DNA Methyltransferase 3b and Association with Development and Prognosis in Gastric Cancer

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Aug 12

PMID 26262893

Citations 7

Authors

Chuan Wang

Zhifang Jia

Donghui Cao

Lili You

Meishan Jin

Xing Wu

Simin Wen

Xueyuan Cao

Jing Jiang

Affiliations

Soon will be listed here.

Abstract

Objective: DNA methyltransferase 3b (DNMT3b) plays an important role in abnormal methylation during tumorigenesis. Polymorphism of the DNMT3b gene may influence DNMT3b activity and be associated with cancer risk. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) of the DNMT3b gene and susceptibility and prognosis of gastric cancer.

Methods: Four hundred and forty-seven histologically-confirmed gastric cancer cases, 111 gastric atrophy cases and 961 tumor-free controls were enrolled into the study. Five tag SNPs (rs6119954, rs1569686, rs4911107, rs4911259 and rs8118663) of the DNMT3b gene were genotyped by TaqMan assay. DNMT3b expression was evaluated in 104 cancer tissues by immunohistochemistry method.

Results: The median follow-up time for 422 gastric patients with prognosis information was 55.1 (51.8-58.5) month. We found that individuals with the rs1569686 variant genotype (TG/GG) were significantly associated with poor prognosis in gastric cancer compared to those carrying the TT genotype (HR = 1.43, 95%CI: 1.02-1.99). This trend was more evident in the long-term survival of gastric cancer. Similar results were observed for the G allele carriers of rs4911107 and T allele carriers of rs4911259 as these two sites were in complete linkage disequilibrium with rs1569686. The rs8118663 GG carriers tended to live shorter than AA/AG genotype (HR = 2.72, 95%CI: 1.45-5.12) in patients living longer than 2.0 years. None of the five SNPs was associated with the risks of gastric cancer or gastric atrophy. And no relationship was found between each of the five SNPs and DNMT3b expression.

Conclusions: This study provides evidence that DNMT3b polymorphisms may predict long-term survival of gastric cancer. However, further studies are needed to reveal the underlying biological roles of DNMT3b polymorphism.

Citing Articles

An updated meta-analysis investigating the association between DNMTs gene polymorphism andgastric cancer risk.

Zhang Y, Wang Y, He M, Chang J PLoS One. 2023; 18(10):e0293466.

PMID: 37878642 PMC: 10599511. DOI: 10.1371/journal.pone.0293466.

Genetic polymorphism in DNMTs and gastric cancer: A systematic review and meta-analysis.

Neves M, Ribeiro J, Medeiros R, Sousa H Porto Biomed J. 2020; 1(5):164-172.

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MicroRNA-421 promotes the proliferation and metastasis of gastric cancer cells by targeting claudin-11.

Yang P, Zhang M, Liu X, Pu H Exp Ther Med. 2017; 14(3):2625-2632.

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DNMT3B -579 G>T Promoter Polymorphism and the Risk of Gastric Cancer in the West of Iran.

Ahmadi K, Soleimani A, Irani S, Kiani A, Ghanadi K, Noormohamadi Z J Gastrointest Cancer. 2017; 49(2):167-171.

PMID: 28220295 DOI: 10.1007/s12029-017-9928-7.

DNA methyltransferase 3A promoter polymorphism is associated with the risk of human spontaneous abortion after assisted reproduction techniques and natural conception.

Liu Y, Zheng H, Guo P, Feng S, Zhou X, Ye D J Assist Reprod Genet. 2016; 34(2):245-252.

PMID: 27817038 PMC: 5306405. DOI: 10.1007/s10815-016-0837-7.

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