title: Association of tumor necrosis factor a-2 and a-8 microsatellite alleles with human papillomavirus and squamous intraepithelial lesions among women in Brazil.
abstract: 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-alpha production allele, the ability of HPV18 to resist the inhibitory effects of TNF-alpha may contribute to the occurrence of infection and consequently to HSIL in women with cervical HPV18 infection.
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo. Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil. rtsimoes@rge.fmrp.usp.br
authors.forename: R T
authors.initials: RT
authors.lastname: Simões
authors.forename: M A G
authors.initials: MA
authors.lastname: Gonçalves
authors.forename: E A
authors.initials: EA
authors.lastname: Donadi
authors.forename: A L
authors.initials: AL
authors.lastname: Simões
authors.forename: J S R
authors.initials: JS
authors.lastname: Bettini
authors.forename: G
authors.initials: G
authors.lastname: Duarte
authors.forename: S M
authors.initials: SM
authors.lastname: Quintana
authors.forename: M W P
authors.initials: MW
authors.lastname: Carvalho
authors.forename: E G
authors.initials: EG
authors.lastname: Soares
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000209:etiology / Q000235:genetics*; D011230:Precancerous Conditions / Q000209:etiology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha