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Journal of Cancer Research and Clinical Oncology

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01-08-2019 | Human Papillomavirus | Original Article – Cancer Research

FOXP3 immunoregulatory gene variants are independent predictors of human papillomavirus infection and cervical cancer precursor lesions

Authors: Fernando Cezar-dos-Santos, Rodolfo Sanches Ferreira, Nádia Calvo Martins Okuyama, Kleber Paiva Trugilo, Michelle Mota Sena, Érica Romão Pereira, Ana Paula Lombardi Pereira, Maria Angelica Ehara Watanabe, Karen Brajão de Oliveira

Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2019

Abstract

Purpose

FOXP3 is a marker of the T regulatory (Treg) cell subset and drives its function and homeostasis. Its expression maintains the host immunosuppressive state that favors persistence of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL) appearance. The present study evaluated the effects of the rs3761548 and rs2232365 intronic single-nucleotide variants (SNVs) and their haplotypes on HPV infection and SIL diagnosis in HPV-infected and -uninfected women.

Methods

HPV DNA-based detection in cervical specimens was performed by PCR. FOXP3 variants were genotyped by PCR-restriction fragment length polymorphism and haplotype recombination sites were inferred for 208 HPV-infected and 218 HPV-uninfected women diagnosed or not with low- or high-grade intraepithelial lesions of cervix. Case–control analyses were carried out by logistic regression adjusted for several socio-demographic, sexual lifestyle, and clinical data.

Results

The homozygous genotype of the rs3761548 variants (A/A) (related to decreased FOXP3 expression) may exert a protective role against HPV infection in women (OR_Aj: 0.60; 95% CI 0.36–0.99; p = 0.049) and was an independent predictor of protection against HSIL development (OR_Adj: 0.28; 95% CI 0.11–0.68; p = 0.006). In addition, the homozygous genotype (G/G) of the rs2232365 variants (related to increased FOXP3 expression) was independently associated with the HPV infection (OR_Adj: 2.10; 95% CI 1.06–4.15; p = 0.033). Haplotype analysis revealed no significant associations in our study.

Conclusions

Our results reveal the significant and independent associations between FOXP3 genetic variants and susceptibility to HPV infection and SIL diagnosis and their role as biomarkers of HPV infection and cervical lesion management.

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Title: FOXP3 immunoregulatory gene variants are independent predictors of human papillomavirus infection and cervical cancer precursor lesions
Authors: Fernando Cezar-dos-Santos
Rodolfo Sanches Ferreira
Nádia Calvo Martins Okuyama
Kleber Paiva Trugilo
Michelle Mota Sena
Érica Romão Pereira
Ana Paula Lombardi Pereira
Maria Angelica Ehara Watanabe
Karen Brajão de Oliveira
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keyword: Human Papillomavirus
Published in: Journal of Cancer Research and Clinical Oncology / Issue 8/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02951-x

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