Case–case comparison of smoking and alcohol risk associations with Epstein–Barr virus-positive gastric cancer
Corresponding Author
M. Constanza Camargo
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Correspondence to: M. Constanza Camargo, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr., BG 9609/6E206, Rockville, MD 20850, USA. Tel: +240-276-7175, Fax: +240-276-7806, E-mail: [email protected]Search for more papers by this authorChihaya Koriyama
Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorKeitaro Matsuo
Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan
Search for more papers by this authorWoo-Ho Kim
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorRoberto Herrera-Goepfert
Department of Pathology, National Cancer Institute, Mexico City, Mexico
Search for more papers by this authorLinda M. Liao
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Search for more papers by this authorthe Eurgast-EPIC Group
Search for more papers by this authorJun Yu
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
Search for more papers by this authorGabriel Carrasquilla
Centro de Estudios e Investigación en Salud, Fundación Santa Fe de Bogotá, Bogotá, Colombia
Search for more papers by this authorJoseph J.Y. Sung
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
Search for more papers by this authorIsabel Alvarado-Cabrero
Servicio de Patología, UMAE Oncología, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Search for more papers by this authorJolanta Lissowska
Division of Cancer Epidemiology and Prevention, M Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
Search for more papers by this authorFernando Meneses-Gonzalez
Programa de Residencia en Epidemiología, Dirección General Adjunta de Epidemiología, Secretaría de Salud, Mexico City, Mexico
Search for more papers by this authorYashushi Yatabe
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
Search for more papers by this authorNan Hu
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Search for more papers by this authorPhilip R. Taylor
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Search for more papers by this authorDouglas R. Morgan
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, TN, USA
Division of Gastroenterology, University of North Carolina, Chapel Hill, NC, USA
Search for more papers by this authorMargaret L. Gulley
Department of Pathology and Laboratory Medicine and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
Search for more papers by this authorJavier Torres
Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Search for more papers by this authorSuminori Akiba
Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorCharles S. Rabkin
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Search for more papers by this authorCorresponding Author
M. Constanza Camargo
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Correspondence to: M. Constanza Camargo, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr., BG 9609/6E206, Rockville, MD 20850, USA. Tel: +240-276-7175, Fax: +240-276-7806, E-mail: [email protected]Search for more papers by this authorChihaya Koriyama
Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorKeitaro Matsuo
Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan
Search for more papers by this authorWoo-Ho Kim
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorRoberto Herrera-Goepfert
Department of Pathology, National Cancer Institute, Mexico City, Mexico
Search for more papers by this authorLinda M. Liao
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Search for more papers by this authorthe Eurgast-EPIC Group
Search for more papers by this authorJun Yu
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
Search for more papers by this authorGabriel Carrasquilla
Centro de Estudios e Investigación en Salud, Fundación Santa Fe de Bogotá, Bogotá, Colombia
Search for more papers by this authorJoseph J.Y. Sung
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
Search for more papers by this authorIsabel Alvarado-Cabrero
Servicio de Patología, UMAE Oncología, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Search for more papers by this authorJolanta Lissowska
Division of Cancer Epidemiology and Prevention, M Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
Search for more papers by this authorFernando Meneses-Gonzalez
Programa de Residencia en Epidemiología, Dirección General Adjunta de Epidemiología, Secretaría de Salud, Mexico City, Mexico
Search for more papers by this authorYashushi Yatabe
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
Search for more papers by this authorNan Hu
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Search for more papers by this authorPhilip R. Taylor
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Search for more papers by this authorDouglas R. Morgan
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, TN, USA
Division of Gastroenterology, University of North Carolina, Chapel Hill, NC, USA
Search for more papers by this authorMargaret L. Gulley
Department of Pathology and Laboratory Medicine and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
Search for more papers by this authorJavier Torres
Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Search for more papers by this authorSuminori Akiba
Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorCharles S. Rabkin
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Search for more papers by this authorAbstract
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.
Abstract
What's new?
Although the H.pylori bacteria is the primary cause of gastric cancer, in some cases the Epstein-Barr virus also appears to be involved. In this study, the authors compared smoking and alcohol use between patients with EBV-positive and EBV-negative gastric cancers. No association was found with alcohol use, but smokers were more likely to have EBV-positive cancer.
REFERENCES
- 1 International Agency for Research on Cancer. Monographs on the evaluation of carcinogenic risks to humans: Schistosomes, liver flukes and Helicobacter pylori, vol. 61. Lyon, France: IARC Press, 1994.
- 2Murphy G, Pfeiffer R, Camargo MC, et al. Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology 2009; 137: 824–33.
- 3 International Agency for Research on Cancer. Monographs on the Evaluation of Carcinogenic Risks to Humans: Epstein-Barr Virus and Kaposi zczc Sarcoma Herpesvirus/Human Herpesvirus 8, vol. 70. Lyon, France: IARC Press, 1997.
- 4Ott G, Kirchner T, Muller-Hermelink HK. Monoclonal Epstein-Barr virus genomes but lack of EBV-related protein expression in different types of gastric carcinoma. Histopathology 1994; 25: 323–9.
- 5Begg CB, Zhang ZF. Statistical analysis of molecular epidemiology studies employing case-series. Cancer Epidemiol Biomarkers Prev 1994; 3: 173–5.
- 6Koriyama C, Akiba S, Minakami Y, et al. Environmental factors related to Epstein-Barr virus-associated gastric cancer in Japan. J Exp Clin Cancer Res 2005; 24: 547–53.
- 7Nakao M, Matsuo K, Ito H, et al. ABO genotype and the risk of gastric cancer, atrophic gastritis, and Helicobacter pylori infection. Cancer Epidemiol Biomarkers Prev 2011; 20: 1665–72.
- 8Zhao JH, Jin HC, Cheung KF, et al. Zinc finger E-box binding factor 1 plays a central role in regulating Epstein-Barr virus (EBV) latent-lytic switch and acts as a therapeutic target in EBV-associated gastric cancer. Cancer Am Cancer Soc 2012; 118: 924–36.
10.1002/cncr.26184 Google Scholar
- 9Kim RH, Chang MS, Kim HJ, et al. Medical history and lifestyle factors contributing to Epstein-Barr virus-associated gastric carcinoma and conventional gastric carcinoma in Korea. Anticancer Res 2010; 30: 2469–75.
- 10Gao Y, Hu N, Han XY, et al. Risk factors for esophageal and gastric cancers in Shanxi Province, China: a case-control study. Cancer Epidemiol 2011; 35: e91–9.
- 11Gonzalez CA, Pera G, Agudo A, et al. Smoking and the risk of gastric cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). Int J Cancer 2003; 107: 629–34.
- 12Chow WH, Swanson CA, Lissowska J, et al. Risk of stomach cancer in relation to consumption of cigarettes, alcohol, tea and coffee in Warsaw, Poland. Int J Cancer 1999; 81: 871–6.
10.1002/(SICI)1097-0215(19990611)81:6<871::AID-IJC6>3.0.CO;2-# CAS PubMed Web of Science® Google Scholar
- 13Campos FI, Koriyama C, Akiba S, et al. Environmental factors related to gastric cancer associated with Epstein-Barr virus in Colombia. Asian Pac J Cancer Prev 2006; 7: 633–7.
- 14Herrera-Goepfert R, Akiba S, Koriyama C, et al. Epstein-Barr virus-associated gastric carcinoma: evidence of age-dependence among a Mexican population. World J Gastroenterol 2005; 11: 6096–103.
- 15Ryan JL, Morgan DR, Dominguez RL, et al. High levels of Epstein-Barr virus DNA in latently infected gastric adenocarcinoma. Lab Invest 2009; 89: 80–90.
- 16Gulley ML, Tang W. Laboratory assays for Epstein-Barr virus-related disease. J Mol Diagn 2008; 10: 279–92.
- 17Japanese Gastric Cancer A. Japanese Classification of Gastric Carcinoma—2nd English Edition. Gastric Cancer 1998; 1: 10–24.
- 18La Torre G, Chiaradia G, Gianfagna F, et al. Smoking status and gastric cancer risk: an updated meta-analysis of case-control studies published in the past ten years. Tumori 2009; 95: 13–22.
- 19Ladeiras-Lopes R, Pereira AK, Nogueira A, et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control 2008; 19: 689–701.
- 20 International Agency for Research on Cancer. Monographs on the Evaluation of Carcinogenic Risks to Humans. A review of human carcinogens: personal habits and indoor combustions, vol. 100E. Lyon, France: IARC Press, 2012.
- 21Ma L, Wang WP, Chow JY, et al. The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or its extract. Gut 2000; 47: 170–7.
- 22Cardenas VM, Graham DY. Smoking and Helicobacter pylori infection in a sample of U.S. adults. Epidemiology 2005; 16: 586–90.
- 23Suzuki T, Matsuo K, Ito H, et al. Smoking increases the treatment failure for Helicobacter pylori eradication. Am J Med 2006; 119: 217–24.
- 24Xu FH, Xiong D, Xu YF, et al. An epidemiological and molecular study of the relationship between smoking, risk of nasopharyngeal carcinoma, and EpsteinBarr virus activation. J Natl Cancer Inst 2012; 104: 1396–410.
- 25Kamper-Jorgensen M, Rostgaard K, Glaser SL, et al. Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph). Ann Oncol 2013 June 19, doi: 10.1093/annonc/mdt218.
- 26Tramacere I, Negri E, Pelucchi C, et al. A meta-analysis on alcohol drinking and gastric cancer risk. Ann Oncol 2012; 23: 28–36.
- 27Bonequi P, Meneses-Gonzalez F, Correa P, et al. Risk factors for gastric cancer in Latin America: a meta-analysis. Cancer Causes Control 2013; 24: 217–31.
- 28Monteiro MG. Alcohol and public health in the Americas. A case for actioned. Pan American Health Organization, Washington, D.C., PAHO, 2007.
- 29Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893–917.
- 30Nagel G, Linseisen J, Boshuizen HC, et al. Socioeconomic position and the risk of gastric and oesophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Epidemiol 2007; 36: 66–76.
- 31Camargo MC, Murphy G, Koriyama C, et al. Determinants of Epstein-Barr virus-positive gastric cancer: an international pooled analysis. Br J Cancer 2011; 105: 38–43.
- 32Lee JH, Kim SH, Han SH, et al. Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis. J Gastroenterol Hepatol 2009; 24: 354–65.
- 33Camargo MC, Kim WH, Chiaravalli AM, et al. Improved survival of gastric cancer with tumour Epstein-Barr virus positivity: an international pooled analysis. Gut 2013 April 12, doi:10.1136/gutjnl-2013-304531.
- 34Schetter AJ, You WC, Lennette ET, et al. Association of Epstein-Barr virus antibody levels with precancerous gastric lesions in a high-risk cohort. Cancer Sci 2008; 99: 350–4.
- 35Levine PH, Stemmermann G, Lennette ET, et al. Elevated antibody titers to Epstein-Barr virus prior to the diagnosis of Epstein-Barr-virus-associated gastric adenocarcinoma. Int J Cancer 1995; 60: 642–4.
- 36Imai S, Koizumi S, Sugiura M, et al. Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein. Proc Natl Acad Sci USA 1994; 91: 9131–5.
- 37Shinkura R, Yamamoto N, Koriyama C, et al. Epstein-Barr virus-specific antibodies in Epstein-Barr virus-positive and -negative gastric carcinoma cases in Japan. J Med Virol 2000; 60: 411–6.
10.1002/(SICI)1096-9071(200004)60:4<411::AID-JMV8>3.0.CO;2-8 CAS PubMed Web of Science® Google Scholar
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