The common cyclooxygenase-2 polymorphism (T8473C) and risk for esophageal adenocarcinoma

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Recent studies have reported overexpression of cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase upregulated in gastrointestinal tissues in response to inflammation, in gastroesophageal reflux disease (GERD), Barrett esophagus (BE) and esophageal adenocarcinoma (EADC). The purpose of this case-control study was to test the hypothesis that the common COX-2 polymorphism (T8473C) is associated with increased risk for EADC. Blood samples were obtained, with informed consent, from patients with GERD (n=126), BE (n=125), and EADC (n=56), defined according to stringent clinico-pathologic criteria. Strictly asymptomatic individuals (n=95) were selected as controls to alleviate the comparison with GERD cases. Following extraction of genomic DNA from blood samples, genotype analysis was performed using a PCR- based primer introduced restriction analysis (PIRA) technique. The frequency of the COX-2 T8473C genotypes (T/T, T/C, C/C) among cases (GERD, BE, or EADC) was compared with the control group using the Chi-square test, and multivariate analysis was performed using logistic regression to adjust for differences in age, gender, smoking and alcohol use. The distribution and frequency of COX-2 T8473C genotypes (T/T, T/C, C/C) for cases and controls is shown in the table. No significant genotypic deviation from the Hardy-Weinberg equilibrium was identified (P = 0.84). Compared with controls, the COX-2 T8473C variant was not associated with an increased risk for GERD (adjusted Odds Ratio [OR] 0.53, 95 % Confidence Interval [95% CI] 0.2-1.38), BE (OR 0.71, 95 % CI 0.27-1.87), or EADC (OR 0.92, 95 % CI 0.25-3.48). We also compared the combined group of asymptomatic controls, GERD and BE cases (n=346) with patients with EADC (n=56), but no significant differences in the distribution of COX-2 genotypes or risk for EADC were seen (P = 0.99; OR 0.98, 95% CI 0.3-3.19).We conclude that the common COX-2 polymorphism (T8473C) is not associated with susceptibility to EADC.

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