Matrix metalloproteinase 2 (MMP2) polymorphism, Helicobacter pylori (HP) infection and esophageal adenocarcinoma (EA) risk

Abstract

10553 Background: Epidemiologic studies suggest that HP infection protects against EA risk, as HP-mediated chronic atrophic gastritis reduces acid reflux. Genetic variations may modify the host response to HP infection and alter this risk. MMP2 expression is commonly upregulated in HP infections. We hypothesize that a functional MMP2 promoter polymorphism (-C1306T) that abolishes a Sp1 binding site and decreases promoter activity will also reduce the protective effects of HP infections in EA risk. Methods: HP status was determined in 98 EA patients and 101 age and gender matched healthy controls, using a commercially available serum immunoblotting kit (Helicoblot 2.1, Genelabs Diagnostics) that measures ever, current, CagA+ and VacA+ HP infections. Genotyping was performed using TaqMan. Data were analyzed using unconditional logistic regression. Results: 39% of cases and 44% of controls (P=0.69) had MMP2 variants (T/T or C/T). 36% of cases and 42% of controls were ever HP infected (P= 0.35). In individuals carrying the MMP2 wild type (CC) genotype, ever HP infection was strongly protective against EA [Odds Ratio (OR) 0.32: 95% CI, 0.13–0.75; P=0.008]. In contrast, in individuals carrying the MMP2 variants that are associated with lower promoter activity, this protective effect was lost (OR 1.76; 95% CI, 0.06–5.2; P= 0.30). Similar results were found when evaluating the MMP2 and current, CagA or VacA infection. Statistical interactions between MMP2 genotype and ever HP infection (P=0.027) and between MMP2 genotype and VacA+ infection (P= 0.035) were significant. Conclusions: We are the first to report that host factors such as the MMP2 polymorphism modulate the role of HP infection in EA susceptibility. No significant financial relationships to disclose.