Abstract
This article introduces a novel risk factor for gastric cancer (GC) by analyzing available epidemiological data from East Asian populations. A significantly higher age-standardized GC rate was observed in Japanese and Korean populations than in Chinese populations, despite nearly identical ethnicity, food habits, obesity rates, and alcohol consumption. Given the pivotal role of environmental factors in GC development, particularly for the intestinal type, a thorough evaluation of the lifestyles of these three populations was conducted to identify commonalities and disparities. It was observed that Japanese and Korean individuals prefer consuming ice water, while Chinese individuals tend to drink warm water, potentially influenced by traditional Chinese medicine disciplines. Considering the key features of GC development, a literature review was conducted to investigate the mechanisms through which the consumption of ice water might contribute to GC initiation and progression. Mechanistically, exposing gastric cells to hypothermia can increase the risk of carcinogenesis through multiple pathways. This includes the promotion of Helicobacter pylori colonization, prolonged gastric inflammation, and mitochondrial dysfunction in gastric cells. Furthermore, drinking ice water can enhance the survival, proliferation, and invasion of GC cells by releasing cold shock proteins, increasing gastric acid secretion, and delaying gastric emptying. Additionally, hypothermia can boost the immune evasion of cancer cells by weakening the antitumor immune system and activating different components of the tumor microenvironment. This paper also explores the association between exposure of GC cells to hypothermia and current insights into cancer hallmarks. These findings may partially elucidate the higher incidence of GC in Japanese and Korean populations and provide a clue for future experimental studies.Graphical abstract available for this article.