Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Int J Cancer. 2014 Feb 15;134(4):948-53. doi: 10.1002/ijc.28402. Epub 2013 Aug 28.
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.
幽门螺杆菌是胃癌的主要病因。然而，在全球范围内，多达 10%的这些肿瘤中存在单克隆 Epstein-Barr 病毒 (EBV) 核酸。EBV 的流行率随着男性、非胃窦部定位和手术破坏的解剖结构而增加。为了进一步研究 EBV 与胃癌之间的关联，我们组织了一个由 11 项研究组成的国际合作，这些研究通过原位杂交评估肿瘤 EBV 状态。我们汇集了 2648 名胃癌患者的个体水平数据，其中 184 名（7%）患有 EBV 阳性癌症；所有研究都有关于吸烟（64%吸烟者）的信息，其中 9 项研究有关于饮酒（57%饮酒者）的信息。我们比较了 EBV 阳性和 EBV 阴性肿瘤患者，以评估吸烟和饮酒与 EBV 状态的相互作用。为了考虑到人群内的聚类，我们使用多水平逻辑回归模型来估计调整性别（72%男性）、年龄（平均 59 岁）、肿瘤组织学（56%Lauren 肠型）、解剖部位（61%非贲门）和诊断年份（1983-2012）分布后的相互作用比值比 (OR)。在未调整的分析中，EBV 阳性与吸烟的 OR 为 2.2（95%CI 1.6-3.2）。通过调整可能的混杂因素，OR 减弱至 1.5（95%CI 1.01-2.3）。EBV 状态与饮酒之间没有显著的相互作用（粗 OR 1.4；调整 OR 1.0）。我们的数据表明，EBV 阳性肿瘤与吸烟相关的胃癌的关联比 EBV 阴性肿瘤更强。相反，与 EBV 状态无关的酒精关联没有变化。EBV 阳性癌症的独特流行病学特征进一步表明病毒是胃癌发生的协同因素。
