Abstract
BackgroundWomen with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL).MethodsPeripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL.ResultsNo significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A.ConclusionsThe −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease.
Highlights
Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of Interleukin 10 (IL-10) at cervix
We investigated whether there is an association between IL-10 promoter polymorphisms and the risk for squamous intraepithelial cervical lesions (SICL) in Mexican women, and whether there is any variation in systemic IL-10 RNA messenger (mRNA) expression level and at cervix level, and the protein level in serum, in the SICL cases with respect non-Cervical Lesions (NCL)
We showed that individuals who are carriers of heterozygous IL-10 -592 C/A polymorphism had a two-fold increased risk of developing SICL
Summary
Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. The fact that only a small proportion of HPV-infected individuals will eventually develop cancer of the cervix and the long latency period between primary infections and cancer emergence suggest that additional factors are involved in the progression. Other factors, such as genetic susceptibility or alteration of the immune response, increase the incidence of HPVassociated lesions [1]. A predominance of the Th2 cytokine profile, in association with a diminished Th1 profile, has been demonstrated in patients with cervical cancer (CC) [2,3,4] This shift from Th1 to Th2 might be responsible for facilitating tumor progression by subverting various cellular immune surveillance mechanisms. An impaired cellular immune response induced by immune suppressor cytokines, such as Interleukin (IL)-10 and Transforming Growth Factor Beta (TGF-β1) has been involved in High Risk HPV (HRHPV) persistence and CC development [2,3,5,6,7]
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