Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control studyReport as inadecuate




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BMC Cancer

, 16:330

Genetics, genomics and epigenetics

Abstract

BackgroundAlterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus HR-HPV and development of premalignant cervical lesions and cervical cancer CC. Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case–control study paired by age.

MethodsPeripheral blood samples from patients with CC n = 200 and hospital controls n = 200, were used to evaluate nine biallelic SNPs of six cytokine genes of the adaptive immune system by allelic discrimination and cytokines serum levels by ELISA.

ResultsAfter analyzing the SNP association by multivariate logistic regression adjusted by age, CC history and smoking history, three Th2 cytokines IL-4, IL-6 and IL-10 and one Th3 TGFB1 cytokine were significantly associated with CC. Individuals with at least one copy of the following risk alleles: T of SNP −590C > T IL-4, C of SNP −573G > C IL-6, A of SNP −592C > A IL-10, T of SNP −819C > T IL-10 and T of SNP −509C > T TGFB1, had an adjusted odds ratio OR of 2.08 95 % CI 1.475–2.934, p = 0.0001, an OR of 1.70 95 % CI 1.208–2.404, p = 0.002, an OR of 1.87 95 % CI 1.332–2.630, p = 0.0001, an OR of 1.67 95 % CI 1.192–2.353, p = 0.003 and an OR of 1.91 95 % CI 1.354–2.701, p = 0.0001, respectively, for CC. The burden of carrying two or more of these risk alleles was found to have an additive effect on the risk of CC p trend = 0.0001. Finally, the serum levels of Th2 and Th3 cytokines were higher in CC cases than the controls; whereas IFNG levels, a Th1 cytokine, were higher in controls than CC cases.

ConclusionThe significant associations of five SNPs with CC indicate that these polymorphisms are potential candidates for predicting the risk of development of CC, representing a risk allelic load for CC and can be used as a biomarker of susceptibility to this disease.

KeywordsGenetic susceptibility profile Cytokines Promoter polymorphisms Serum levels Cervical neoplasm  Download fulltext PDF



Author: K. Torres-Poveda - A. I. Burguete-García - M. Bahena-Román - R. Méndez-Martínez - M. A. Zurita-Díaz - G. López-Estra

Source: https://link.springer.com/







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