Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>A (rs5743336), TLR4 3725G>C (rs11536889), FAS 1377G>A (rs2234767), FAS 670A>G (rs1800682) and FASL 844T>C (rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for NOD1 796G/G genotype to be associated with increased risk of HRAG (62.4% vs. 54.5% in controls, p = 0.082). FAS 670G/G genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (p = 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. NOD1 796G>A and TLR4 3725G>C gene polymorphisms were also not associated with Helicobacter pylori infection.ACE, NOD1, TRL4 and FAS/FASL gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.Based on the current paradigm, gastric carcinogenesis is considered as multistep process involving complex interplay between Helicobacter pylori (H. pylori) infection, environmental and host genetic factors [1]. In gastric carcinogenesis two distinct pathways have been suggested for intestinal and diffuse type of gastric cancer (GC) (1). Correa et al. [2] demonstrated that H. pylori infection induces chronic inflammation of the gastric mucosa, leading to atrophic gastritis (AG) and intestinal metaplasia (IM), which are regarded as essential predisposing factors in intestinal-type GC development. Many researchers have shown a close relationship between H. pylori not only for intestinal-type GC, but also for diffuse-type GC [3,4]. Furthermore, although AG and IM are considered as obligatory predisp