72-P: IFNG+874 AA GENOTYPE IS AN IMPORTANT RISK FACTOR FOR THE DEVELOPMENT OF INVASIVE CERVICAL CANCER (CC) IN MEXICAN WOMEN

Abstract

Cervical carcinogenesis is a multifactorial process that involves genetic and environmental factors and results from a crosstalk of HPV infected cells and the host cellular immune esponse (CIR). The purpose of the study was to search for the role of IFNG+874(A/T) alleles and genotypes may play in the establishment of invasive CC in Mexican Mestizo women. A total of 55 patients with invasive CC and 213 controls with normal PAP smears, all of them with the same ethnicity, were included in the study. DNA was obtained from peripheral blood samples using the Maxwell16 instrument (Promega). For allele discrimination of the IFNG (+874A/T) rs2430561, a Taqman real time PCR assay was used on the ABI 7500 Real-Time PCR System (Life Technologies Foster City, CA). Susceptibility was found associated with IFNG (+874A/T) SNP in CC. The A allele (OR=2.1; CI 1.1-3.9; p=0.02) and the corresponding AA genotype (OR=2.23; CI (1.1-4.4); p=0.02) were significantly increased in the patients group and the TT genotype was not deviated at all. Interestingly, this genotype was absent in the patients. The allele distribution was under Hardy Weinberg expectation among the healthy controls. The data shown here demonstrate the involvement of the A allele and of the AA genotype in the risk of developing invasive CC in Mexican Mestizo women. The A allele is responsible of low IFNg production and its effect is recessive, since the GF of the AT genotype is not increased in the patients group (23.64% patient Vs. 37.50% controls).The AA genotype was also found associated with susceptibility in Chinese, Brazilian and Indian women with CC and its association was confirmed by a meta-analysis that included 17 case-control studies. It is well known, that a lower production of IFNg may impair the development of an effective protective CIR, which is relevant to clear the HPV from the infected cells, being the persistence of HPV infection crucial in favoring progression of low grade lesions to CC.