Determinants of Epstein-Barr virus-positive gastric cancer: an international pooled analysis

Br J Cancer. 2011 Jun 28;105(1):38-43. doi: 10.1038/bjc.2011.215. Epub 2011 Jun 7.


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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / virology*
  • Aged
  • Carcinoma, Signet Ring Cell / genetics
  • Carcinoma, Signet Ring Cell / virology*
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Herpesvirus 4, Human / genetics*
  • Humans
  • International Agencies
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / virology*