STAT3 polymorphism and Helicobacter pylori CagA strains with higher number of EPIYA-C segments independently increase the risk of gastric cancer

BMC Cancer

Research Article

Viviane C Fernandes¹  Adriana D Gomes¹  Kádima N Teixeira¹  Dulciene Maria Magalhães Queiroz¹  Kátia S Brito¹  Sérgio A Batista¹  Gifone A Rocha¹  César LL Faria¹  Nathálie BF Almeida¹  Andreia MC Rocha¹  Fabrício F Melo¹ 

[1] Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil;

关键词: Gastric cancer;    STAT;    STAT;    Helicobacter pylori;    CagA;    EPIYA-C segments;   

DOI  :  10.1186/s12885-015-1533-1

 received in 2015-03-05, accepted in 2015-07-02,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundBecause to date there is no available study on STAT3 polymorphism and gastric cancer in Western populations and taking into account that Helicobacter pylori CagA EPIYA-C segment deregulates SHP-2/ERK-JAK/STAT3 pathways, we evaluated whether the two variables are independently associated with gastric cancer.MethodsWe included 1048 subjects: H. pylori-positive patients with gastric carcinoma (n = 232) and with gastritis (n = 275) and 541 blood donors. Data were analyzed using logistic regression model.ResultsThe rs744166 polymorphic G allele (p = 0.01; OR = 1.76; 95 % CI = 1.44-2.70), and CagA-positive (OR = 12.80; 95 % CI = 5.58-19.86) status were independently associated with gastric cancer in comparison with blood donors. The rs744166 polymorphism (p = 0.001; OR = 1.64; 95 % CI = 1.16-2.31) and infection with H. pylori CagA-positive strains possessing higher number of EPIYA-C segments (p = 0.001; OR = 2.28; 95 % CI = 1.41-3.68) were independently associated with gastric cancer in comparison with gastritis. The association was stronger when host and bacterium genotypes were combined (p < 0.001; OR = 3.01; 95 % CI = 2.29-3.98). When stimulated with LPS (lipopolysaccharide) or Pam3Cys, peripheral mononuclear cells of healthy carriers of the rs744166 GG and AG genotypes expressed higher levels of STAT3 mRNA than those carrying AA genotype (p = 0.04 for both). The nuclear expression of phosphorylated p-STAT3 protein was significantly higher in the antral gastric tissue of carriers of rs744166 GG genotype than in carriers of AG and AA genotypes.ConclusionsOur study provides evidence that STAT3 rs744166 G allele and infection with CagA-positive H. pylori with higher number of EPIYA-C segments are independent risk factors for gastric cancer. The odds ratio of having gastric cancer was greater when bacterium and host high risk genotypes were combined.

【 授权许可】

Unknown   
© Rocha et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.