Helicobacter pylori, chronic atrophic gastritis, inactive aldehyde dehydrogenase-2, macrocytosis and multiple upper aerodigestive tract cancers and the risk for gastric cancer in alcoholic Japanese men

Background: Gastric carcinoma occurs at a high rate in alcoholic Japanese men. Inactive heterozygous aldehyde dehydrogenase‐2 (ALDH2*1/2*2) and macrocytosis (mean corpuscular volume [MCV] ≥ 106 fl) enhance the risk for esophageal carcinoma, which frequently occurs with gastric carcinoma in this population. Whether alcoholism affects Helicobacter pylori‐induced chronic atrophic gastritis (CAG) is unknown. Methods: This study of Japanese alcoholic men with (n = 45) and without (n = 281) gastric carcinoma included assessment of H. pylori IgG antibody, serum pepsinogen‐confirmed CAG, MCV, and ALDH2 genotype. Results: The gastric carcinoma cases had a significantly higher age‐adjusted prevalence of H. pylori‐positivity (78%vs 57%), CAG (78%vs 42%), ALDH2*1/2*2 (36%vs 14%), MCV ≥106 fl (38%vs 20%), and concurrent esophageal/oropharyngolaryngeal carcinoma (18%vs 5%) than controls. Among gastric cancer‐free controls, the prevalence of CAG was higher than generally reported in Japan, regardless of H. pylori status (H. pylori‐positive, 56%vs 35–36% for Japanese general population; H. pylori‐negative, 8%vs 1–3%). Alcoholism may accelerate the progression of CAG. Each of these factors increased the risk of gastric carcinoma (ORs = 3.7 for H. pylori‐positive, 2.7 for non‐severe CAG, 8.7 for severe CAG, 3.5 for ALDH2*1/2*2, 2.5 for MCV ≥106 fl, and 3.7 for concurrent carcinoma). A multivariate analysis showed that CAG and ALDH2*1/2*2 were independently related to the risk of gastric carcinoma. Combinations of CAG and ALDH2*1/2*2 showed greater risks of gastric carcinoma (ORs = 4.0 for non‐severe CAG alone, 17.6 for severe CAG alone, 9.7 for ALDH2*1/2*2 alone, 17.1 for non‐severe CAG plus ALDH2*1/2*2, and 39.2 for severe CAG plus ALDH2*1/2*2). Conclusions: Combining blood tests for H. pylori, CAG, MCV and ALDH2 genotype could offer a new means of predicting risk of gastric carcinoma in Japanese alcoholic men.