Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location

Gastroenterology. 2009 Sep;137(3):824-33. doi: 10.1053/j.gastro.2009.05.001. Epub 2009 May 13.


Background & aims: Epstein-Barr virus (EBV) has been causally associated with cancer; some gastric carcinomas have a monoclonal EBV genome in every cancer cell, indicating that they arose from a single infected progenitor cell. However, the proportion of EBV-positive gastric carcinomas is uncertain, and the etiologic significance is unknown.

Methods: We conducted a meta-analysis of 70 studies including 15,952 cases of gastric cancer assessed by in situ hybridization for EBV-encoded small RNA.

Results: The pooled prevalence estimate of EBV positivity was 8.7% (95% confidence interval [CI]: 7.5%-10.0%) overall, with a 2-fold difference by sex: 11.1% (95% CI: 8.7%-14.1%) of gastric cancer cases in males vs 5.2% (95% CI: 3.6%-7.4%) of cases in females. Tumors arising in the gastric cardia (13.6%) or corpus (13.1%) were more than twice as likely to be EBV-positive as those in the antrum (5.2%; P < .01 for both comparisons). EBV prevalence was 4 times higher (35.1%) for tumors in postsurgical gastric stump/remnants. Over 90% of lymphoepithelioma-like carcinomas were EBV positive, but only 15 studies reported any cases of this type; prevalence did not significantly differ between the more common diffuse (9.5%) [corrected] and intestinal (7.6%) [corrected] histologies. EBV prevalence was similar in cases from Asia (8.3%), Europe (9.2%), and the Americas (9.9%).

Conclusions: EBV-positive gastric cancers greatly differ from other gastric carcinomas based on sex, anatomic subsite, and surgically disrupted anatomy, indicating that it is a distinct etiologic entity. Epidemiologic studies comparing EBV-positive and -negative gastric cancers are warranted to investigate EBV's role in gastric carcinogenesis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / virology
  • Carcinoma / virology
  • Cardia / virology
  • Epstein-Barr Virus Infections / complications
  • Female
  • Gastric Stump
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Male
  • Pyloric Antrum / virology
  • Sex Factors
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Stomach Neoplasms / virology*