Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population
[Background] Inflammation is a key factor in the process of carcinogenesis from chronic gastritis induced by Helicobacter pylori. Selenoprotein S (SEPS1) is involved in the control of the inflammatory response in the endoplasmic reticulum (ER).
Recently the -105G>A polymorphism in the promoter of SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined the association between this polymorphism and the risk of gastric cancer.[Methods] We took stomach biopsies during endoscopies of 268 Japanese gastric cancer patients (193 males and 75 females, average age 65.3), and 306 control patients (184 males and 122 females, average age 62.7) and extracted the DNA from the biopsy specimens.
All subjects provided written informed consent. For the genotyping of the SEPS1 promoter polymorphism at position -105G>A, PCR-RFLP methods were used and the PCR products were digested with PspGI.
Logistic-regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, sex, and H. pylori infection status.[Results] Among cases, the distribution of genotypes was as follows: 88.4% were GG, 11.2% were GA, and 0.4% were AA.
Among controls, the distribution was as follows: 92.5% were GG, 7.2% were GA, and 0.3% were AA. Among males, carrying the A allele was associated with an increased odds of gastric cancer, compared with the GG genotype (OR: 2.0, 95% CI 1.0-4.1, p=0.07).
Compared with the GG genotype, carrying the A allele was significantly associated with increased risks of intestinal type gastric cancer (OR: 2.0, 95%CI 1.0-3.9, p<0.05) as well as of gastric cancer located in the middle third of the stomach (OR: 2.0, 95%CI 1.0-3.9, p<0.05).[Conclusions] The -105G>A promoter polymorphism of SEPS1 was associated with the intestinal type of gastric cancer. This polymorphism may influence the inflammatory conditions of gastric mucosa.
Larger population-based studies are needed for clarifying the relation between inflammatory responses and SEPS1 polymorphism.
Author: Tomoyuki Shibata, Tomiyasu Arisawa, Tomomitsu Tahara, Masaaki Ohkubo, Daisuke Yoshioka, Naoko Maruyama, Hiroshi Fujita, Yoshio Kamiya, Masakatsu Nakamura, Mitsuo Nagasaka, Masami Iwata, Kazuya Takahama, Makoto Watanabe and Ichiro Hirata
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Published on: 2009-01-13
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