title: Multiplex H. pylori Serology and Risk of Gastric Cardia and Noncardia Adenocarcinomas.
abstract: The reported associations with gastric adenocarcinoma and seropositivity to different Helicobacter pylori antigens using multiplex serology have not been consistent across studies. We aimed to investigate the association between 15 different multiplex serology antigens and the risk of gastric cardia (GCA) and gastric noncardia (GNCA) adenocarcinomas in northeastern Iran, a population with high rates of gastric adenocarcinoma. We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 27 unspecified) and 524 controls who were individually matched to cases for age, sex, and place of residence in a population-based case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA. Ninety-five percent of controls were seropositive to H. pylori. Of the 15 antibodies in the multiplex assay, 11 showed no significant association with gastric adenocarcinomas. CagA and VacA were associated with a significantly increased risk of all gastric adenocarcinoma and GNCA in multivariate models. Surprisingly, GroEL and NapA were significantly associated with a reduced risk of these tumors. Only CagA antigen was associated with significantly elevated risk of GCA. We found no associations between H. pylori seropositivity overall either by whole-cell ELISA test or multiplex serology, likely due to the high prevalence of seropositivity. Individual antigen testing showed that CagA positivity was associated with increased risk of both noncardia and cardia adenocarcinoma, which is similar to some other Asian populations, whereas two antigens were associated with lower risk of gastric cancer. This latter result was unexpected and should be retested in other populations.
authors.affiliation: Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Shakeri
authors.affiliation: Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. abnetc@mail.nih.gov malek@ams.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.affiliation: Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Dariush
authors.initials: D
authors.lastname: Nasrollahzadeh
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: German Cancer Research Center, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawilta
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Gwen
authors.initials: G
authors.lastname: Murphy
authors.affiliation: Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. American Cancer Society, Atlanta.
authors.forename: Farhad
authors.initials: F
authors.lastname: Islami
authors.affiliation: Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Sotoudeh
authors.affiliation: German Cancer Research Center, Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Michel
authors.affiliation: Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Arash
authors.initials: A
authors.lastname: Etemadi
authors.affiliation: German Cancer Research Center, Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.affiliation: Digestive Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Poustchi
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Institute for Translational Epidemiology and Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York.
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
authors.affiliation: Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland.
authors.forename: Farin
authors.initials: F
authors.lastname: Kamangar
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. abnetc@mail.nih.gov malek@ams.ac.ir.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
mesh_terms: D000230:Adenocarcinoma / Q000382:microbiology*; D000368:Aged; D000942:Antigens, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000097:blood; D002299:Cardia / Q000382:microbiology* / Q000473:pathology*; D016022:Case-Control Studies; D018834:Chaperonin 60 / Q000097:blood; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016481:Helicobacter Infections / Q000453:epidemiology*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D050901:Nitrate Reductase / Q000097:blood; D012307:Risk Factors; D012698:Serologic Tests; D013274:Stomach Neoplasms / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; C080866:cagA protein, Helicobacter pylori; D050901:Nitrate Reductase