title: Determinants of Epstein-Barr virus-positive gastric cancer: an international pooled analysis.
abstract: BACKGROUND
  Meta-analyses of the published literature indicate that about 9% of gastric cancers contain Epstein-Barr virus (EBV), with consistent and significant differences by sex and anatomic subsite. This study aimed to identify additional determinants of EBV positivity and their joint effects.
  
  
  METHODS
  From 15 international populations with consistent laboratory testing for EBV, we pooled individual-level data for 5081 gastric cancer cases including information on age, sex, subsite, histologic type, diagnostic stage, geographic region, and period of diagnosis. First, we combined population-specific EBV prevalence estimates using random effects meta-analysis. We then aggregated individual-level data to estimate odds ratios of EBV positivity in relation to all variables, accounting for within-population clustering.
  
  
  RESULTS
  In unadjusted analyses, EBV positivity was significantly higher in males, young subjects, non-antral subsites, diffuse-type histology, and in studies from the Americas. Multivariable analyses confirmed significant associations with histology and region. Sex interacted with age (P=0.003) and subsite (P=0.002) such that male predominance decreased with age for both subsites. The positivity of EBV was not significantly associated with either stage or time period.
  
  
  CONCLUSIONS
  Aggregating individual-level data provides additional information over meta-analyses. Distinguishing histologic and geographic features as well as interactions among age, sex, and subsite further support classification of EBV-associated gastric cancer as a distinct aetiologic entity.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard., Rockville, MD 20852, USA. camargomc@mail.nih.gov
authors.forename: M C
authors.initials: MC
authors.lastname: Camargo
authors.forename: G
authors.initials: G
authors.lastname: Murphy
authors.forename: C
authors.initials: C
authors.lastname: Koriyama
authors.forename: R M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: W H
authors.initials: WH
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Herrera-Goepfert
authors.forename: A H
authors.initials: AH
authors.lastname: Corvalan
authors.forename: E
authors.initials: E
authors.lastname: Carrascal
authors.forename: A
authors.initials: A
authors.lastname: Abdirad
authors.forename: M
authors.initials: M
authors.lastname: Anwar
authors.forename: Z
authors.initials: Z
authors.lastname: Hao
authors.forename: J
authors.initials: J
authors.lastname: Kattoor
authors.forename: E
authors.initials: E
authors.lastname: Yoshiwara-Wakabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Eizuru
authors.forename: C S
authors.initials: CS
authors.lastname: Rabkin
authors.forename: S
authors.initials: S
authors.lastname: Akiba
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000821:virology*; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007390:International Agencies; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000821:virology*