Abstract 3834: Difference of host immunity and mucosal defense to <i>H. pylori</i> infection caused Asian paradox on incidence of gastric cancer: Correlation with mucosal mRNA expression of <i>IL-8</i>, pepsinogenI/II ratio, and <i>H. pylori cagA</i> gene mutation in Thai and Japanese gastric cancer
Authors: Sirikan Yamada, Shunji Kato, Takeshi Matsuhisa, Luksana Makonkawkeyoon, Thiraphat Charkrabandhu, Pawit Sutharat, Nirush Lertprasertsuk, Masaru Miki, Norio Matsukura, Masao Miyashita, Nobutaka Yamada, Masaru Yoshida, Bandhuphat Chakrabandhu, Worawit Khangtragool, Trichak Sundhu, Takashi Tajiri, Takeshi Azuma
Journal: Cancer Research (2010)

Abstract Background: Recent in vitro studies showed the association between mucosal mRNA expression of IL-8 with cagA, East Asian type in gastric cancer that frequently found in Japanese. In Thais, not only gastric cancer, but also gastroduodenal ulcer incidences are opposite to those in Japanese. We hypothesized that an associations difference between Thais and Japanese stomach mucosal tissue cytokine response to H. pylori infection may lead us to find key role of host defense in gastric carcinogenesis. Method: There were 143 non-cancer volunteers in Thais, and 110 Thai and Japanese gastric cancer patients who underwent endoscopy and gastric surgery. IL-8 cytokine mRNA expression was conducted by real time RT-PCR. Histopathology, serum IgG antibody for H. pylori, pepsinogen I and II were tested. Tissue H. pylori DNA extracted from antral position in stomach was genotyped for cagA mutation. p value &amp;lt;0.05 was considered as a statistically significant. Result: No distribution difference by sex, age, and stage of advance cancer in both nations. H. pylori positivity in Thai gastric cancer was 70.5% (55/78). There is a significant lower PGI/II ratio in Japanese than in Thai gastric cancer, p = 0.026. Thai gastric cancer patients had significantly lower level of PGII/II ratio at means of 3.3±1.7 than in normal one, p =0.042, and of other non-chronic active gastritis (CAG), p =0.002. Means level of IL-8 mRNA expression in Thai cancer and Japanese cancer were 8511.36±5.22 and 174.54±329.51, respectively. Means level of IL-8 mRNA expression in Thai cancer group is also higher than in non-cancer group, p = 0.058. In subgroup analysis, we could not see a significantly differences of IL-8 mRNA expression or PGI/II ratio in positivity and true negativity H. pylori infection. However, in positive cases with less than 2.0 of PGI/II low ratio showed a significant higher level of IL-8 expressions than with PGI/II ratio over 3.0, p &amp;lt; 0.05. In Thai non-cancer, cagA genotype yield of 33 per cent each of Eastern, Western, and Mix type. Low PGI/II ratio did not associate to CAG severity score in Thais. There was only 32/55 (58%) who had positive H. pylori by PCR and pathology with a rising up of H. pylori IgG antibody. In the 6-year followed up of Thai CAG group with H. pylori cagA, Eastern infection, no one develop to be cancer. Conclusion: In this vivo study, we postulated that IL-8 cytokine expression is a predictive marker for poor prognosis incidence in gastric cancer. There is also association to low PGI/II ratio. The opposite result on IL-8 mRNA expression between both nations reflex to individualized host stomach mucosal defense. High level IL-8 mRNA expression in Thais showed mucosal defense in gastric cancer carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3834.