High Salt Intake in Helicobacter Pylori Infected Individuals Can Significantly Increase the Risk of Gastric Cancer; a Global Analysis

Abstract

The odds ratio with 95%CIs was used to evaluated the synergistic effects between high salt intake and H. pylori infection among gastric cancer cases. Heterogeneity was assessed by I2 index and Cochrane Q-test; In addition, the presence of publication bias was measured using Begg’s p-value and Egger’s p-value test (18). There were 7 studies met our criteria. These studies were conducted during 2003-2019 in Korea, Japan, United states, China, and Portugal. We evaluated data of 8,068 cases. H. pylori infection was confirmed by ELISA and UBT in these eligible studies (Table 1). The frequency of gastric cancer in habitual high salt intakes with positive H. pylori infection was significantly greater than those preference salty food with negative H. pylori infection (Chi-square: 5.33; p-value: 0.02). Our results suggested that there is a positive association between high salt intake and risk of gastric cancer in H. pylori infected-individuals (OR: 1.47; 95%CI: 1.01-2.15; p-value: 0.04; I2: 83.6; Q-value: 36.6; Begg’s p-value: 0.13; Egger’s p-value: 0.25) (Fig. 1). Gastric cancer is one of the top cause of cancer-related death in the world (1). Unfortunately, gastric cancer has a poor-prognosis and untreated early gastric cancer lesions will progress to advanced gastric cancer during 4-5 years (2). Gastric cancer is a heterogeneous malignancy with multifactorial causes including socio-economic status, diet, environmental condition, genetic polymorphism as well as infectious agents particularly chronic infection by Helicobacter pylori (3). In 1994, the International Agency for Research on Cancer (IARC) announced that H. pylori is considered as class I carcinogens and etiologic cause of human gastric cancer (4). However, a high rate of H. pylori infection in areas with a low incidence of gastric cancer remains an enigma (5). It has been suggested that H. pylori infection alone cannot cause gastric cancer without synergistic effects of lifestyle, diet, etc (6-7). On the other hand, there is evidence that dietary salt has an association with gastric adenocarcinoma (8-9). Therefore, it may that H. pylori infection and high salt intakes have synergistic effects in the development of gastric cancer. the previous studies reveal that salt cause upregulation of H. pylori cagA gene during in vitro experiments (10). We performed a comprehensive literature search in several databases including PubMed, Scopus, Embase, and Google scholar using search terms consisting “Helicobacter pylori”, “Salt”, “Gastric cancer”, “Dietary” and “Salt intake” without limitation in time and language. The potential relevant documents were evaluated and the required data such as first author, publication year, country, total cases, the frequency of high salt intake among H. pylori-infected cases with gastric cancer or odds ratio corresponding 95% confidence intervals (95%CIs), and H. pylori diagnostic test were summarized in Table 1. The odds ratio with 95%CIs was used to evaluate the synergistic effects between high salt intake and H. pylori infection among gastric cancer cases. Heterogeneity was assessed by I2 index and Cochrane Q-test; In addition, the presence of publication bias was measured using Begg’s p-value and Egger’s p-value test (18).   There were 7 case-control studies that met our criteria. These studies were conducted during 2003-2019 in Korea, Japan, United states, China, and Portugal. We evaluated data of 8,068 cases. H. pylori infection was confirmed by ELISA and UBT in these eligible studies (Table 1). The sodium concentration was assessed by history, urinary sodium, as well as Food frequency questionnaires (FFQs) in these studies.The frequency of gastric cancer in habitual high salt intakes with positive H. pylori infection was significantly greater than those who preference salty food with negative H. pylori infection (Chi-square: 5.33; p-value: 0.02). Our results suggested that there is a positive association between high salt intake and risk of gastric cancer in H. pylori infected-individuals (OR: 1.47; 95%CI: 1.01-2.15; p-value: 0.04; I2: 83.6; Q-value: 36.6; Begg’s p-value: 0.13; Egger’s p-value: 0.25) (Fig 1). Tsugane et al, 2004 were suggested that there is a significant relation between salt intake and the subsequent risk of gastric cancer in a Japanese population (19). In addition, Ge et al., 2012 provided a systematic review to show the association between Habitual dietary salt intake and risk of developing to gastric cancer using 11 retrospective single-center studies (20).