Case-case comparison of smoking and alcohol risk associations with Epstein-Barr virus-positive gastric cancer
Case-case comparison of smoking and alcohol risk associations with Epstein-Barr virus-positive gastric cancer
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DOI：
10.1002/ijc.28402
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发表时间：
2014-02-01
影响因子：
6.4
通讯作者：
Rabkin, Charles S.
中科院分区：
文献类型：
--
作者：
Camargo, M. Constanza;Koriyama, Chihaya;Rabkin, Charles S.
幽门螺杆菌是导致胃癌的主要原因。然而，单克隆EB病毒（EBV）核酸也存在于全球高达10%的这些肿瘤中。男性、非胃窦定位和手术破坏的解剖结构会增加EBV的患病率。为了进一步研究EB病毒与胃癌之间的关系，我们组织了一个国际联盟的11项研究，肿瘤EB病毒状态进行原位杂交评估。我们汇总了2，648名胃癌患者的个体水平数据，其中包括184名（7%）EBV阳性癌症患者;所有研究都有吸烟信息（64%吸烟者），9项研究有酒精数据（57%饮酒者）。我们比较了EBV阳性和EBV阴性肿瘤患者，以评估吸烟和酒精与EBV状态的相互作用。为了解释人群内聚类，使用多水平logistic回归模型估计根据性别（72%男性）、年龄（平均59岁）、肿瘤组织学（56% Lauren泌尿系型）、解剖亚部位（61%非贲门）和诊断年份（1983-2012年）分布调整的相互作用比值比（OR）。在未调整的分析中，吸烟与EB病毒阳性的OR为2.2 [95%置信区间（CI）1.6-3.2]。通过调整可能的混杂因素，OR降至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;校正OR 1.0）。我们的数据表明，吸烟与胃癌的关系在EBV阳性的肿瘤中比EBV阴性的肿瘤更强。相反，与酒精的零关联不因EBV状态而异。EBV阳性癌症的独特流行病学特征进一步暗示病毒作为胃癌发生的辅助因子。
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.