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, non-antral 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 9 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, multi-level 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 co-factor in gastric carcinogenesis.

Effect of expressions of tumor necrosis factor α and interleukin 1B on peritoneal metastasis of gastric cancer

“…Approximately 990,000 people around the world are diagnosed with GC each year, of whom about 738,000 die from this disease [2]. Helicobacter pylori infection is the primary cause of GC incidence, and several lifestyles are independently associated with GC risk, such as alcohol, smoking, and weight [3,4]. Curative surgeries and adjuvant chemotherapies are considered as acceptable intervention for GC treatment [5,6].…”

Epstein-Barr Virus-Associated Gastric Carcinoma: Use of Host Cell Machineries and Somatic Gene Mutations

“…Camargo et al [14] recently reported that smoking is a risk factor for EBVaGC (odds ratio of 1.5; 95% CI 1.01-2.3). The frequency of Helicobacter pylori infection is controversial; some reports indicate less frequent H. pylori infection in EBVaGC [15,16], while others indicate that the infection frequency is higher in EBVaGC than in other gastric cancers [17,18].…”

Profiles of Epstein-Barr Virus Associated Gastric Carcinomas in Brunei Darussalam

“…High salt intake is a proven risk factor and high salt intake is also common in our population. Smoking has also been shown to have an impact; more on EBV related than non EBV related gastric cancers (Camargo et al, 2014). H. pylori infection is a common infection among our population (Chong VH et al, 2009) and this may attenuate the impact of EBV on gastric carcinogenesis.…”

“…However, earlier cases showed more lymphocytic infiltrations consistent with what have been reported in the literature. A recent large multi-center study reported that EBVaGC tended to have lower tumor-node-metastasis based on the TNM staging system and EBV positivity was associated with better survival (Camargo et al, 2014). Although, studies have shown that EBV lead to molecular changes resulting in gastric carcinogenesis, different to that of H. pylori sequence, and that there are certain characteristics that are unique to EBVaGC, there are still differences and conflicting results based on studies from other populations.…”