Dietary factors in Helicobacter pylori -negative early gastric cancer: Risk, protection, and mechanistic insights

Helicobacter pylori (H. pylori )-negative early gastric cancer (GC) is an emerging clinical and epidemiological challenge that cannot be explained by the classical H. pylori -driven carcinogenic pathway. Growing evidence indicates that dietary factors play a critical role in modulating gastric mucosal integrity, inflammation, and carcinogenic progression in the absence of H. pylori infection. High salt intake and processed foods, particularly those rich in nitrates and nitrites, are associated with mucosal injury, oxidative stress, and endogenous N-nitroso compound formation, thereby increasing early GC risk. In contrast, diets rich in fruits, vegetables, antioxidants, and dietary fiber exert protective effects by reducing oxidative DNA damage, attenuating chronic inflammation, and supporting a favorable gastric microenvironment. Mediterranean and prudent dietary patterns, characterized by plant-based foods, polyphenols, and unsaturated fatty acids, show inverse associations with GC risk independent of H. pylori status. While vitamins C and E demonstrate consistent protective trends, evidence regarding vitamin D remains inconclusive due to population heterogeneity. Emerging studies using the dietary inflammatory index further suggest that pro-inflammatory diets may promote H. pylori -negative gastric carcinogenesis. This minireview summarizes current evidence and highlights key mechanistic gaps to inform targeted prevention strategies in high-risk populations.