title: Case-case comparison of smoking and alcohol risk associations with Epstein-Barr virus-positive gastric cancer.
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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
authors.forename: M Constanza
authors.initials: MC
authors.lastname: Camargo
authors.forename: Chihaya
authors.initials: C
authors.lastname: Koriyama
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Woo-Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Roberto
authors.initials: R
authors.lastname: Herrera-Goepfert
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liao
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Gabriel
authors.initials: G
authors.lastname: Carrasquilla
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.forename: Isabel
authors.initials: I
authors.lastname: Alvarado-Cabrero
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Fernando
authors.initials: F
authors.lastname: Meneses-Gonzalez
authors.forename: Yashushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Ti
authors.initials: T
authors.lastname: Ding
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Morgan
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Gulley
authors.forename: Javier
authors.initials: J
authors.lastname: Torres
authors.forename: Suminori
authors.initials: S
authors.lastname: Akiba
authors.forename: Charles S
authors.initials: CS
authors.lastname: Rabkin
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects*; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013274:Stomach Neoplasms / Q000209:etiology*
keywords: EBV; alcohol; gastric cancer; pooled-analysis; smoking
references.citation: J Med Virol. 2000 Apr;60(4):411-6
references.pmid: 10686024
references.citation: IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt E):1-538
references.pmid: 23193840
references.citation: Br J Cancer. 2011 Jun 28;105(1):38-43
references.pmid: 21654677
references.citation: Cancer Sci. 2008 Feb;99(2):350-4
references.pmid: 18201267
references.citation: Int J Epidemiol. 2007 Feb;36(1):66-76
references.pmid: 17227779
references.citation: Cancer Causes Control. 2008 Sep;19(7):689-701
references.pmid: 18293090
references.citation: World J Gastroenterol. 2005 Oct 21;11(39):6096-103
references.pmid: 16273633
references.citation: J Mol Diagn. 2008 Jul;10(4):279-92
references.pmid: 18556771
references.citation: Gastroenterology. 2009 Sep;137(3):824-33
references.pmid: 19445939
references.citation: Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9131-5
references.pmid: 8090780
references.citation: Gastric Cancer. 1998 Dec;1(1):10-24
references.pmid: 11957040
references.citation: Epidemiology. 2005 Jul;16(4):586-90
references.pmid: 15951682
references.citation: Histopathology. 1994 Oct;25(4):323-9
references.pmid: 7835837
references.citation: J Natl Cancer Inst. 2012 Sep 19;104(18):1396-410
references.pmid: 22972969
references.citation: Cancer Epidemiol Biomarkers Prev. 1994 Mar;3(2):173-5
references.pmid: 8049640
references.citation: J Gastroenterol Hepatol. 2009 Mar;24(3):354-65
references.pmid: 19335785
references.citation: Tumori. 2009 Jan-Feb;95(1):13-22
references.pmid: 19366050
references.citation: Int J Cancer. 1995 Mar 3;60(5):642-4
references.pmid: 7860138
references.citation: Anticancer Res. 2010 Jun;30(6):2469-75
references.pmid: 20651410
references.citation: Int J Cancer. 2010 Dec 15;127(12):2893-917
references.pmid: 21351269
references.citation: J Exp Clin Cancer Res. 2005 Dec;24(4):547-53
references.pmid: 16471317
references.citation: IARC Monogr Eval Carcinog Risks Hum. 1997;70:1-492
references.pmid: 9705682
references.citation: Am J Med. 2006 Mar;119(3):217-24
references.pmid: 16490464
references.citation: Cancer. 2012 Feb 15;118(4):924-36
references.pmid: 21717425
references.citation: Gut. 2000 Aug;47(2):170-7
references.pmid: 10896906
references.citation: Ann Oncol. 2013 Sep;24(9):2245-55
references.pmid: 23788758
references.citation: Gut. 2014 Feb;63(2):236-43
references.pmid: 23580779
references.citation: Cancer Epidemiol Biomarkers Prev. 2011 Aug;20(8):1665-72
references.pmid: 21680535
references.citation: Ann Oncol. 2012 Jan;23(1):28-36
references.pmid: 21536659
references.citation: Int J Cancer. 2003 Nov 20;107(4):629-34
references.pmid: 14520702
references.citation: Lab Invest. 2009 Jan;89(1):80-90
references.pmid: 19002111
references.citation: IARC Monogr Eval Carcinog Risks Hum. 1994;61:1-241
references.pmid: 7715068
references.citation: Cancer Epidemiol. 2011 Dec;35(6):e91-9
references.pmid: 21846596
references.citation: Cancer Causes Control. 2013 Feb;24(2):217-31
references.pmid: 23224270
references.citation: Int J Cancer. 1999 Jun 11;81(6):871-6
references.pmid: 10362132
references.citation: Asian Pac J Cancer Prev. 2006 Oct-Dec;7(4):633-7
references.pmid: 17250442