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

• Published in: British journal of cancer 2011-06, Vol.105 (1), p.38-43
• Main Authors: Camargo, M C, Murphy, G, Koriyama, C, Pfeiffer, R M, Kim, W H, Herrera-Goepfert, R, Corvalan, A H, Carrascal, E, Abdirad, A, Anwar, M, Hao, Z, Kattoor, J, Yoshiwara-Wakabayashi, E, Eizuru, Y, Rabkin, C S, Akiba, S
• Format: Article
• Language: English
• Subjects: 631/67/1858; 631/67/2324; 692/699/67/1504/1829; Adenocarcinoma - genetics; Adenocarcinoma - virology; Age; Aged; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Signet Ring Cell - genetics; Carcinoma, Signet Ring Cell - virology; Clinical Study; Drug Resistance; Epidemiology; Epstein-Barr virus; Epstein-Barr Virus Infections - genetics; Epstein-Barr Virus Infections - virology; Female; Gastric cancer; Herpesvirus 4, Human - genetics; Histology; Humans; Infections; Infectious diseases; International Agencies; Lymphoma; Male; Medical research; Medical sciences; Meta-analysis; Meta-Analysis as Topic; Middle Aged; Molecular Medicine; Oncology; Pathology; Preventive medicine; Prognosis; Stomach Neoplasms - genetics; Stomach Neoplasms - virology; Tumors; Viral diseases
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.215

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.