Variantes genéticas na região promotora da ciclooxigenase 2 (cox2) e susceptibilidade ao câncer gástrico no Peru

Abstract

Inflammation of the gastric mucosa is an important factor in the development of gastric cancer, and it is believed that the enzyme cyclooxygenase 2 (encoded by the COX2 gene) participates in the inflammatory process, helping to repair the lesion in the gastric mucosa. Thus, the expression of COX2 would be beneficial to the gastric mucosa. However, several studies suggest that overexpression of COX2 due to polymorphisms increases the risk of developing gastric cancer. Several studies conducted in other populations have demonstrated the association between SNPs in the promoter region of COX2 gene with gastric cancer. For this reason, the objective of this work was to test whether these genetic variants are associated with gastric cancer in the Peruvian population, noting that Peru is the country with the highest rates of incidence and mortality of this cancer in Latin America. To achieve this goal, we developed a methodology that allowed us to obtain the following results: 1) 6 SNPs were identified in the promoter region of COX2 gene in individuals of the indigenous population, 3 of which are also present in Europeans and Africans (rs20417, rs689465 and rs689466), and 3 are new variants, (2) 10 common haplotypes were estimated, and haplotype and nucleotide diversity in Amerindians was higher than that of Europeans and smaller than that of Africans. The DL was higher (87%) between rs20417 and rs689465 in Europeans, that Amerindians (72%) and Africans (15%). According to the value of the FST, all three populations differ significantly, and according to the neutrality tests it was confirmed the null hypothesis of mutation drift equilibrium, (3) we selected two informative SNPs rs689466 and rs689465, the latter one being a tagSNP, (4) genotypes were determined and the allele frequencies for the two informative SNPs, in 225 patients with gastric cancer and 352 controls from a mixed population of Peru for association test, and in Amerindians of different ethnicities (17 Quechuas, 50 Shimaas and 52 Ashaninkas) to evaluate whether these frequencies differ from the mixed population, (5) in association analysis was obtained OR=1.15; 95%CI:0.85-1.57 for rs689465, and OR=0.93; 95%CI:0.73-1.19 for rs689466, these results indicate that there is no association of these variants with gastric cancer. This is the first study that characterizes genetic variants of the promoter region of COX2 gene in Peruvian Amerindians and its pattern of genetic diversity, and tests the association of these variants with gastric cancer in the admixture Peruvian population, finding no association in the population evaluated in this study.