MMP1 1G/2G promoter polymorphism and risk of esophageal adenocarcinoma

Abstract

10555 Background: The 2G allele of the MMP1 -1607 1G/2G promoter polymorphism creates an Ets binding site that leads to increased transcriptional and enzyme activity, particularly in the presence of growth factors and cytokines. This polymorphism has been associated with greater risk of cancer (e.g., renal cell, lung and oral cancers, glioblastomas) and cancer invasiveness (e.g., melanoma, cervical, lung and colorectal cancer). The aim of the current study was to evaluate the role of this MMP 1G/2G polymorphism in the risk of esophageal adenocarcinoma (EA). Methods: We evaluated 323 histologically confirmed EA cases and 464 healthy controls frequency-matched for age and gender. Genotyping of the MMP1 1G/2G promoter polymorphism involved a Taqman approach. All EAs had endoscopic evidence showing that the center of the tumors were located at or above the gastroesophageal junction. Odds Ratios (OR) were calculated using multivariate logistic regression, adjusted for age, gender, smoking status, and body-mass index (BMI) at the age of 18 years (to represent a healthy adult BMI). Results: Genotype frequencies were: 33% (1G/1G), 47% (1G/2G) & 20% (2G/2G) in controls; in cases, 26% (1G/1G), 50% (1G/2G) & 24% (2G/2G). 88% of cases were male. The MMP1 2G/2G and 1G/2G genotypes conferred a greater risk of EA, with adjusted ORs of 1.50 (95%CI=1.0–2.3) and 1.34 (95%CI=0.9–1.9), respectively, when compared with the wildtype 1G/1G genotype. The 2G allele (2G/2G + 1G/2G) conferred an adjusted OR of 1.38 (95%CI=1.0–1.9). By stage, the adjusted ORs for the 2G allele were 1.26 (95%CI=0.8–2.1), 1.45 (95%CI=0.9–2.3), & 1.54 (95%CI=0.9–2.7) for node negative, node-positive, and metastatic disease, respectively. Conclusions: The 2G allele of the MMP1 -1607 1G/2G polymorphism was associated with an increased risk of EA in this analysis. In addition, there was a non-significant trend towards conferring greater risk in the more advanced stages of EA, suggesting a possible role of this polymorphism in the invasiveness of this cancer. No significant financial relationships to disclose.