title: Helicobacter pylori blood biomarker for gastric cancer risk in East Asia.
abstract: Incidence and mortality rates for gastric cancer, the fifth most commonly diagnosed and third most deadly cancer worldwide, are highest in East Asia. We sought to identify gastric cancer risk biomarkers among eight prospective studies from China, Japan and Korea.
  
  
  
  This pooled nested case-control study included 1608 incident non-cardia gastric cancer cases and 1958 matched controls. Pre-diagnostic antibody levels to 15 Helicobacter pylori proteins were assessed using multiplex serology. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
  
  
  
  Sero-positivity to 10 H. pylori antigens (Omp, CagA, VacA, HcpC, HP 0305, GroEL, NapA, HyuA, Cad, HpaA) was associated with a 1.29- to 3.26-fold increase in odds of gastric cancer. Omp and HP 0305 consistently remained associated with gastric cancer risk after mutually adjusting for all other markers. Sero-positivity to both Omp and HP 0305 was associated with an over 4-fold increase in gastric cancer incidence (OR, 4.09; 95% CI 3.26-5.13). When limited to only those who are CagA+ H. pylori+, Omp/HP 0305 sero-positivity remained strongly associated with an over 3-fold increase in the odds of gastric cancer (OR, 3.34; 95% CI 2.27-4.91). The results were highly consistent among the cohorts.
  
  
  
  We have confirmed new H. pylori biomarkers that are strongly associated with gastric cancer risk, even among those infected with the known H. pylori virulence factor CagA. These results may help to design cost-efficient prevention strategies to reduce gastric cancer incidence in East Asia.
authors.affiliation: Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Vanderbilt Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DFKZ), Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Michel
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Gwen
authors.initials: G
authors.lastname: Murphy
authors.affiliation: Epidemiology and Prevention Group, National Cancer Center, Tokyo, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Sasazuki
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.affiliation: Department of Cancer Epidemiology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
authors.affiliation: Cancer Research Institute, Department of Biomedical Sciences and Department of Preventive Medicine.
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.affiliation: Department of Epidemiology and Health Promotion, Institute for Health Promotion, Yonsei University, Seoul, Korea.
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Jee
authors.affiliation: Department of Epidemiology and Health Promotion, Institute for Health Promotion, Yonsei University, Seoul, Korea.
authors.forename: Eo Rin
authors.initials: ER
authors.lastname: Cho
authors.affiliation: Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Jeongseon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Vanderbilt Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Sheau-Chiann
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.affiliation: Epidemiology and Prevention Group, National Cancer Center, Tokyo, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
authors.affiliation: Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DFKZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center meira.epplein@vanderbilt.edu.
authors.forename: Meira
authors.initials: M
authors.lastname: Epplein
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005202:Asia, Eastern / Q000453:epidemiology; D005260:Female; D016481:Helicobacter Infections / Q000097:blood* / Q000453:epidemiology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers
keywords: East Asia; Helicobacter pylori; biomarkers; gastric cancer; stomach neoplasms