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Background: Helicobacter pylori infection is a well-known risk factor for gastric cancer. However, the contribution of germline pathogenic variants in cancer-predisposing genes and their effect, when combined with H. pylori infection, on the risk of gastric cancer has not been widely evaluated., Methods: We evaluated the association between germline pathogenic variants in 27 cancer-predisposing genes and the risk of gastric cancer in a sample of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan. We also assessed the combined effect of pathogenic variants and H. pylori infection status on the risk of gastric cancer and calculated the cumulative risk in 1433 patients with gastric cancer and 5997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC)., Results: Germline pathogenic variants in nine genes ( APC , ATM , BRCA1 , BRCA2 , CDH1 , MLH1 , MSH2 , MSH6 , and PALB2 ) were associated with the risk of gastric cancer. We found an interaction between H. pylori infection and pathogenic variants in homologous-recombination genes with respect to the risk of gastric cancer in the sample from HERPACC (relative excess risk due to the interaction, 16.01; 95% confidence interval [CI], 2.22 to 29.81; P = 0.02). At 85 years of age, persons with H. pylori infection and a pathogenic variant had a higher cumulative risk of gastric cancer than noncarriers infected with H. pylori (45.5% [95% CI, 20.7 to 62.6] vs. 14.4% [95% CI, 12.2 to 16.6])., Conclusions: H. pylori infection modified the risk of gastric cancer associated with germline pathogenic variants in homologous-recombination genes. (Funded by the Japan Agency for Medical Research and Development and others.)., (Copyright © 2023 Massachusetts Medical Society.)

Helicobacter pylori infection is a significant risk factor for gastric cancer. The infection is acquired mainly in early childhood and is influenced by environmental factors, including socioeconomic status and sibling number. However, the impact of socioeconomic status and sibling number on Helicobacter pylori infection has not been well studied in Japan. We conducted a cross-sectional study to evaluate the impact of socioeconomic status, represented by education level, and sibling number on the prevalence of Helicobacter pylori infection among 3,423 non-cancer subjects who visited Aichi Cancer Center between 2005 and 2013. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using a logistic regression model adjusted for potential confounding variables. Of the 3,423 subjects, 1,459 (42.6%) were Helicobacter pylori -positive. The prevalence of Helicobacter pylori infection linearly decreased with increasing socioeconomic status [ORs (95% CIs) of moderate and high socioeconomic status relative to low socioeconomic status of 0.67 (0.53-0.84) and 0.43 (0.34-0.54), respectively; P trend=9.7×10 -17 ]. In contrast, the prevalence of Helicobacter pylori infection linearly increased with increasing sibling number [ORs (95% CIs) of SN 3-4 and ≥5 relative to sibling number ≤2 of 1.74 (1.47-2.06) and 2.54 (2.12-3.04), respectively; P trend=1.2×10 -24 ]. This study showed that socioeconomic status and sibling number were significantly associated with the prevalence of Helicobacter pylori infection., Competing Interests: The authors have nothing to disclose.

Background: In Helicobacter pylori-driven gastric cancer, mucosal colonization induces chronic inflammation that may variably progress to cancer. Prospective studies of circulating inflammation-related proteins have suggested weak associations with gastric cancer risk. To assess potential utility as a screening tool in clinical settings, we examined circulating levels of a wide range of key inflammation molecules for associations with early-stage gastric cancer., Methods: We used pretreatment EDTA plasma from 239 individuals with early-stage noncardia gastric cancer (203 stage I and 36 stage II) and 256 age-frequency-matched H. pylori-seropositive cancer-free controls within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 92 biomarkers were measured by proximity extension assays using Olink's Proseek Immuno-oncology Panel. Odds ratios (ORs) for association with gastric cancer risk were calculated for quantiles (two to four categories) of each biomarker from unconditional logistic regression models, adjusted for age, sex, smoking and alcohol consumption. Two-sided P values <0.05 were considered as significant. The false discovery rate (FDR) was used to correct for multiple comparisons., Results: Of 83 evaluable biomarkers, lower levels of TNFRSF12A (per quartile OR, 0.82; nominal P-trend = 0.02) and ADGRG1 (per quartile OR, 0.84; nominal P-trend = 0.03) were associated with early-stage gastric cancer but were not statistically significant after FDR correction., Conclusion: Our study did not identify any inflammation-related biomarkers that may be useful for early disease detection. To date, this is the first assessment of circulating inflammation-related proteins in early-stage gastric cancer. Given the complex inflammation processes preceding malignant transformation, further investigation of other biomarkers is warranted., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45-1.33), 0.65 (0.30-1.39), 1.03 (0.38-2.79), and 0.84 (0.22-3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30-3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00-3.86), 1.92 (0.74-4.95), and 5.80 (1.12-30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma.