This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Simões, R. T. Articles by Soares, E. G. Search for Related Content PubMed PubMed Citation Articles by Simões, R. T. Articles by Soares, E. G.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, August 2005, p. 3932-3937, Vol. 43, No. 8
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.8.3932-3937.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Association of Tumor Necrosis Factor a-2 and a-8 Microsatellite Alleles with Human Papillomavirus and Squamous Intraepithelial Lesions among Women in Brazil

R. T. Simões,^1* M. A. G. Gonçalves,^2* E. A. Donadi,² A. L. Simões,³ J. S. R. Bettini,¹ G. Duarte,⁴ S. M. Quintana,⁴ M. W. P. Carvalho,³ and E. G. Soares¹

Pathology Department,¹ Division of Clinical Immunology,² Department of Gynecology and Obstetrics,⁴ Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil³

Received 16 December 2004/ Returned for modification 17 January 2005/ Accepted 20 May 2005

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk factor for cervical cancer. Tumor necrosis factor (TNF) is a pluripotent cytokine that plays an important role in inhibiting the action of microbial agents, and TNF microsatellite polymorphisms have been associated with several diseases, including cancer and viral infections. This study analyzed the associations between TNFa to -e microsatellite polymorphisms and the severity of squamous intraepithelial lesions (SIL), according to the presence of the oncogenic HPV16 and HPV18 types. Samples from 146 HPV-positive women with low-grade SIL (LSIL) and high-grade SIL (HSIL) and samples from 101 healthy women were studied. TNF microsatellite polymorphism typing and HPV detection and typing were performed using PCR-amplified DNA hybridized with sequence-specific primers. Data were analyzed by Fisher's exact test using the GENEPOP software. Significant associations were observed between LSIL and the TNFa-8 allele (4/166; P = 0.04), as well as between TNFa-2 with HPV18 only (16/44; P = 0.002) and TNFa-2 with HPV18 coinfection with HPV16 (16/44; P = 0.001). Patients exhibiting the TNFa-2 allele and harboring HPV18, in the presence or absence of coinfection with HPV16, had an increased risk of HSIL occurrence (13/38; P = 0.04; 5/10; P = 0.04) compared to patients with other HPV types. These results suggest that the TNFa-8 allele is associated with increased susceptibility to the occurrence of LSIL and that despite the presence of a high TNF- production allele, the ability of HPV18 to resist the inhibitory effects of TNF- may contribute to the occurrence of infection and consequently to HSIL in women with cervical HPV18 infection.

---

* Corresponding author. Mailing address for Renata Simões: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo. Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil. Phone: 55 16 602-3179. Fax: 55 16 633-1068. E-mail: rtsimoes{at}rge.fmrp.usp.br. Mailing address for Maria Alice Guimarães Gonçalves: Division of Clinical Immunology, School of Medicine of Ribeirão Preto, University of São Paulo. Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil. Phone: 55 16 602-3179. Fax: 55 16 633-1068. E-mail: epigin{at}uol.com.br.

---

Journal of Clinical Microbiology, August 2005, p. 3932-3937, Vol. 43, No. 8
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.8.3932-3937.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.