Nrf2 gene promoter polymorphism and gastric carcinogenesis

Background/Aims: Three gene polymorphisms of Nrf2, which regulate the expression of detoxifying and antioxidant genes, have been identified. We attempted to clarify the relationship of these polymorphisms with the carcinogenesis in the stomach. Methodology: The study was performed in 209 patients with gastric cancer and 198 patients with no evidence of gastric malignancies on upper gastroduodenal endoscopy. We employed PCR-SSCP method to detect gene polymorphisms. Results: Overall, both polymorphisms at position of -686/-684 and -650 were not significant risk factors of carcinogenesis in the stomach. However, the -686/-684 A/G allele carrier had a significantly reduced risk for gastric carcinogenesis (p=0.022), especially of diffuse type (p=0.020), in H. pylori-negative cases. The activity and inflammation scores in Nrf2 -686/-684 A/G carriers were significantly lower than those in the non-A/G carriers (p=0.038 and p=0.019, respectively). Conclusions: The -686/-684 haplotype of Nrf2 gene may be associated with the development of gastric inflammation and with gastric carcinogenesis without the influence of H. pylori infection, although overall association with gastric carcinogenesis seems to be none.