Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location.
OBJECTIVE
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.
Murphy
Gwen
G
Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, NIH, Rockville, Maryland 20892, USA. murphygw@mail.nih.gov
Pfeiffer
Ruth
R
Camargo
M Constanza
MC
Rabkin
Charles S
CS
D000230:Adenocarcinoma / Q000821:virology; D002277:Carcinoma / Q000821:virology; D002299:Cardia / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D018530:Gastric Stump; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D011706:Pyloric Antrum / Q000821:virology; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000473:pathology / Q000601:surgery / Q000821:virology*