Abstract 4808: Case-case comparison of smoking and alcohol risk associations with Epstein-Barr virus-positive gastric cancer.
Authors: Camargo M. Constanza , Koriyama Chihaya , Matsuo Keitaro , Kim Woo-Ho , Herrera-Goepfert Roberto , Liao Linda M. , Gonzalez Carlos , Yu Jun , Sung Joseph , Lissowska Jolanta , Meneses-Gonzalez Fernando , Yatabe Yashushi , Gulley Margaret , Akiba Suminori , Rabkin Charles S. 
Published: August 2014

Abstract
BACKGROUND AND AIMS: Although the bacterium Helicobacter pylori is the primary cause of gastric cancer, monoclonal Epstein-Barr virus (EBV) nucleic acid is present in 8-10% of these tumors worldwide. Viral prevalence is increased with male sex, non-antral subsite localization and surgically disrupted anatomy. To further examine associations between EBV and gastric cancer with sufficient statistical power, we have organized an international consortium of multiple studies with consistent tumor testing by in situ hybridization. Here we compare data on EBV-positive and EBV-negative gastric cancers to identify behavioral risk factors. METHODS: From eight case-control studies (four from Asia, two from Europe and two from Latin America), we pooled individual-level data for aggregated analysis of 1545 gastric cancer cases, including 152 (9.8%) that were EBV-positive. We assessed associations with cigarette (61% smokers) and alcohol (69% drinkers) use in case-case comparisons –rather than the original case-control approach– to account for possible interactions with tumor-specific characteristics. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multi-level logistic regression to control for within-population clustering. ORs were adjusted (aOR) for distributions of sex (67% male), age (mean 60 years), educational attainment (44% secondary school or greater), body-mass index (49% obese, WHO Classification), tumor histology (63% Lauren intestinal-type) and anatomic subsite (85% noncardia). RESULTS: In unadjusted analyses, the OR for tumor EBV positivity among smokers was 2.4 (95% CI, 1.6-3.6) overall with no substantially difference between current and former smokers (respective ORs, 2.4 and 2.5). The association was attenuated by adjustment for the possible confounders but remained statistically significant (aOR, 1.6; 95% CI, 1.01-2.5). There was a crude association of tumor EBV positivity with drinking (OR, 1.8; 95% CI, 1.02-3.3) that was explained by smoking and the other confounders (aOR, 1.1; 95% CI, 0.6-2.1). CONCLUSIONS: The association of cigarette smoking with gastric cancer may be stronger for EBV-positive than EBV-negative tumors. Conversely, the null association of gastric cancer with alcohol drinking does not apparently vary by EBV status. Distinct epidemiologic characteristics of EBV-positive gastric cancer further implicate the virus as an etiologic co-factor in gastric carcinogenesis.
Citation Format: M. Constanza Camargo, Chihaya Koriyama, Keitaro Matsuo, Woo-Ho Kim, Roberto Herrera-Goepfert, Linda M. Liao, Carlos Gonzalez, Jun Yu, Joseph Sung, Jolanta Lissowska, Fernando Meneses-Gonzalez, Yashushi Yatabe, Margaret Gulley, Suminori Akiba, Charles S. Rabkin. Case-case comparison of smoking and alcohol risk associations with Epstein-Barr virus-positive gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4808. doi:10.1158/1538-7445.AM2013-4808