Case–case comparison of smoking and alcohol risk associations with Epstein–Barr virus‐positive gastric cancer |
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| Authors: | M. Constanza Camargo Chihaya Koriyama Keitaro Matsuo Woo‐Ho Kim Roberto Herrera‐Goepfert Linda M. Liao the Eurgast‐EPIC Group Jun Yu Gabriel Carrasquilla Joseph J.Y. Sung Isabel Alvarado‐Cabrero Jolanta Lissowska Fernando Meneses‐Gonzalez Yashushi Yatabe Ti Ding Nan Hu Philip R. Taylor Douglas R. Morgan Margaret L. Gulley Javier Torres Suminori Akiba Charles S. Rabkin |
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| Affiliation: | 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA;2. Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan;3. Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan;4. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea;5. Department of Pathology, National Cancer Institute, Mexico City, Mexico;6. Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China;7. Centro de Estudios e Investigación en Salud, Fundación Santa Fe de Bogotá, Bogotá, Colombia;8. Servicio de Patología, UMAE Oncología, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico;9. Division of Cancer Epidemiology and Prevention, M Sklodowska‐Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland;10. Programa de Residencia en Epidemiología, Dirección General Adjunta de Epidemiología, Secretaría de Salud, Mexico City, Mexico;11. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan;12. Shanxi Cancer Hospital, Taiyuan, Shanxi, China;13. Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, TN, USA;14. Division of Gastroenterology, University of North Carolina, Chapel Hill, NC, USA;15. Department of Pathology and Laboratory Medicine and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA;16. Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico |
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| Abstract: | Helicobacter pylori is the primary cause of gastric cancer. However, monoclonal Epstein–Barr virus (EBV) nucleic acid is also present in up to 10% of these tumors worldwide. EBV prevalence is increased with male sex, nonantral localization and surgically disrupted anatomy. To further examine associations between EBV and gastric cancer, we organized an international consortium of 11 studies with tumor EBV status assessed by in situ hybridization. We pooled individual‐level data on 2,648 gastric cancer patients, including 184 (7%) with EBV‐positive cancers; all studies had information on cigarette use (64% smokers) and nine had data on alcohol (57% drinkers). We compared patients with EBV‐positive and EBV‐negative tumors to evaluate smoking and alcohol interactions with EBV status. To account for within‐population clustering, multilevel logistic regression models were used to estimate interaction odds ratios (OR) adjusted for distributions of sex (72% male), age (mean 59 years), tumor histology (56% Lauren intestinal‐type), anatomic subsite (61% noncardia) and year of diagnosis (1983–2012). In unadjusted analyses, the OR of EBV positivity with smoking was 2.2 [95% confidence interval (CI) 1.6–3.2]. The OR was attenuated to 1.5 (95% CI 1.01–2.3) by adjustment for the possible confounders. There was no significant interaction of EBV status with alcohol drinking (crude OR 1.4; adjusted OR 1.0). Our data indicate the smoking association with gastric cancer is stronger for EBV‐positive than EBV‐negative tumors. Conversely, the null association with alcohol does not vary by EBV status. Distinct epidemiologic characteristics of EBV‐positive cancer further implicate the virus as a cofactor in gastric carcinogenesis. |
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| Keywords: | alcohol EBV gastric cancer smoking pooled‐analysis |
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