This study aims to explore the relationship between soy food consumption and gastric cancer (GC) risk, accounting for Helicobacter pylori infection status. We analyzed data from patients with GC and healthy individuals prospectively enrolled by 6 hospitals between 2016 and 2018. Dietary intake was evaluated using questionnaires that categorized seven dietary habits and 19 food groups. Multivariate logistic regression models were applied to examine associations. Model I adjusted for various epidemiological factors, while Model II included further adjustments for H. pylori infection. Primary exposures examined were consumption frequencies of nonfermented, unsalted soy foods (soybean/tofu) and fermented, salty soy foods (soybean paste stew). A total of 5,535 participants were included, with 1,629 diagnosed with GC. In Model I, the frequency of soybean/tofu consumption was inversely related to GC risk; adjusted odd ratios (aORs) were 0.62 (95% confidence interval [CI], 0.48-0.8), 0.38 (95% CI, 0.3-0.49), 0.42 (95% CI, 0.33-0.53), and 0.33 (95% CI, 0.27-0.42) for 1 time/week, 2 times/week, 3 times/week, and ≥4 times/week. Consumption of 2 servings/week of soybean paste stew showed the lowest GC association, forming a V-shaped curve. Both low (aOR, 4.03; 95% CI, 3.09-5.26) and high serving frequencies of soybean paste stew (aOR, 2.23; 95% CI, 1.76-2.82) were associated with GC. The association between soy foods and GC in Model II was similar to that in Model I. The soy food-GC associations were consistent across sexes in Model I. Nonetheless, the positive correlation between frequent consumption of soybean paste stew (≥5 times/week) and GC was more pronounced in women (aOR, 7.58; 95% CI, 3.20-17.99) compared to men (aOR, 3.03; 95% CI, 1.61-5.88) in Model II. Subgroup analyses by H. pylori status and salty diet revealed a consistent inverse relationship between soybean/tofu and GC risk. In contrast, soybean paste stew showed a V-shaped relationship in H. pylori-positive or salty diet groups and no significant association in the H. pylori-negative group. Soybean/tofu intake is consistently associated with a decreased risk of GC. However, the relationship between soybean paste stew consumption and GC risk varies, depending on H. pylori infection status and dietary salt intake. ClinicalTrials.gov Identifier: NCT03046745.
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