Synergistic Promoting Effects of Helicobacter pylori Infection and High‐salt Diet on Gastric Carcinogenesis in Mongolian Gerbils

Abstract

Helicobacter pylori (Hp) infection and high-salt diet administration are both considered to be important factors in gastric carcinogenesis in man. To investigate the interaction of these two factors on gastric carcinogenesis, an experimental study of the carcinogenesis model was performed. Mongolian gerbils were treated with 20 ppm of N-methyl-N-nitrosourea (MNU) in their drinking water for alternate weeks for a total of 5 weeks' exposure (groups 1, 2, 3 and 4) or were maintained as controls (groups 5, 6, 7 and 8). At week 11, the animals were inoculated with Hp (groups 1, 2, 5 and 6) or the vehicle alone (groups 3, 4, 7 and 8), and after week 12, animals were fed a 10% high salt diet (groups 1, 3, 5 and 7) or the control diet (groups 2, 4, 6 and 8). At week 50, the incidence of adenocarcinomas in group 1 (32.1%, 6 well-differentiated, 2 poorly-differentiated adenocarcinomas, and one signet-ring cell carcinoma) was significantly higher than in groups 3 (0%) (P < < < <0.005) and 4 (0%) (P < < < <0.01). The incidence of adenocarcinomas in group 2 (11.8%, one well-differentiated adenocarcinoma, and one signet-ring cell carcinoma) was also higher than in groups 3 and 4. A high-salt diet enhanced the effects of Hp infection on gastric carcinogenesis, and these two factors acted synergistically to promote the development of stomach cancers. Moreover, Hp infection promoted gastric carcinomas more than the high-salt diet.

Sodium Intake, Salt Taste and Gastric Cancer Risk According to Helicobacter Pylori Infection, Smoking, Histological Type and Tumor Site in China

“…The proposed mechanisms which salt can cause gastric cancer either direct damage to the gastric mucosa leading to hyperplasia of the gastric pit epithelium with increased potential for mutations or effect of interaction with H.pylori, as the damage caused by salt may also increase gastric H.pylori colonization (Nozaki et al, 2002;Yang, 2006). This suggests there may be interaction between sodium intake and H.pylori infection, and this was confirmed in our study.…”

Diet and the risk of gastric cancer: review of epidemiological evidence

“…Although salted food intake may increase the risk of H. pylori infection, salt per se was shown to act synergistically and dose-dependently to promote the development of gastric adenocarcinoma in Mongolian gerbils treated with N-methyl-N-nitrosourea (MNU) [32,33]. A synergistic exacerbatory effect of H. pylori infection and salted food intake has also been reported in case-control studies in Japan [34] and Korea [23].…”

Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis

“…Although we could not observe significant differences in smoking habits or the H. pylori-negative rate between the high-and low-JA intake groups, we cannot exclude the possibility of a secondary association with other unidentified lifestyle factors. Furthermore, the questionnaire in our study did not include an assessment of daily sodium intake for each subject, although high sodium intake enhances gastric mucosal inflammation and is thought to be involved in stomach carcinogenesis as a cancer promoter (Nozaki et al, 2002). However, a simple questionnaire for sodium preference is by no means a reliable indicator of sodium intake in healthy subjects or hypertensive patients (Ohta et al, 2004;Hashimoto et al, 2008).…”

“…However, the overall, H. pylori antibody titers were lower, and in particular, they were significantly lower as compared with that in the low-intake group among the non-elderly (o65 years old) subjects. In general, higher H. pylori antibody titers correlate with more active H. pylorirelated CAG, as shown in clinical and animal studies (Eaton and Krakowka, 1992;Shimizu et al, 1999;Loffeld et al, 2000;Nozaki et al, 2002). In particular, in H. pylori-infected Mongolian gerbils, higher antibody titers are associated not only with more active gastritis, but also with a higher incidence of gastric cancer (Shimizu et al, 1999).…”

“…Environmental factors, particularly lifestyle and dietary habits, are the most frequent and direct factors to which the gastric mucosa is exposed and have a major effect on gastric carcinogenesis. For example, high sodium intake increases gastric mucosal inflammation and the risk of gastric cancer (Nozaki et al, 2002;Shikata et al, 2006), and cigarette smoking is considered to be deeply involved in the transition of CAG to intestinal metaplasia and dysplasia (Kneller et al, 1992;Tredaniel et al, 1997), which are precancerous conditions, in a model of gastric carcinogenesis postulated by Correa (Correa and Houghton, 2007). Conversely, animal experiments and epidemiological studies have shown that vegetables, fruits and green tea lower the risk of gastric cancer (Yu et al, 1995;Kobayashi et al, 2002).…”