title: Oncogenic CagA promotes gastric cancer risk via activating ERK signaling pathways: a nested case-control study.
abstract: BACKGROUND
  CagA cellular interaction via activation of the ERK signaling pathway may be a starting point in the development of gastric cancer. This study aimed to evaluate whether genes involved in ERK downstream signaling pathways activated by CagA are susceptible genetic markers for gastric cancer.
  
  
  METHODS
  In the discovery phase, a total of 580 SNPs within +/-5 kbp of 30 candidate genes were genotyped to examine an association with gastric cancer risk in the Korean Multi-center Cancer Cohort (100 incident gastric cancer case-control sets). The most significant SNPs (raw or permutated p value<0.02) identified in the discovery analysis were re-evaluated in the extension phase using unconditional logistic regression model (400 gastric cancer case-control sets). Combined analyses including pooled- and meta-analysis were conducted to summarize all the results.
  
  
  RESULTS
  24 SNPs in eight genes (ERK, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk) were significantly associated with gastric cancer risk in the individual SNP analyses in the discovery phase (p<0.05). In the extension analyses, ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 showed marginally significant gene-dose effects for gastric cancer. Consistently, final combined analysis presented the SNPs as significantly associated with gastric cancer risk (OR = 1.56, [95% CI: 1.19-2.06], OR = 0.61, [95% CI: 0.43-0.87], OR = 0.59, [95% CI: 0.54-0.76], respectively).
  
  
  CONCLUSIONS
  Our findings suggest that ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 are genetic determinants in gastric carcinogenesis.
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Yang
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Cho
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Ma
authors.forename: Kwang-Pil
authors.initials: KP
authors.lastname: Ko
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.forename: Bo Youl
authors.initials: BY
authors.lastname: Choi
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Han
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Song
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Soung-Hoon
authors.initials: SH
authors.lastname: Chang
authors.forename: Hai-Rim
authors.initials: HR
authors.lastname: Shin
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D009857:Oncogenes; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D048049:Extracellular Signal-Regulated MAP Kinases