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Sousa H.,Portuguese Institute of Oncology of Porto | Sousa H.,University of Porto | Sousa H.,Instituto Portugues Of Oncologia Do Porto Fg | Oliveira S.,Portuguese Institute of Oncology of Porto | And 6 more authors.
Tumor Biology | Year: 2014

Tumour necrosis factor alpha (TNF-α) is a strong pro-inflammatory cytokine with important functions on immune response to viral infections. A single nucleotide polymorphism on the -308 position of the promoter region of TNFA gene characterised by a G > A transition has been associated with different TNF-α levels and therefore with differential susceptibility for the development several diseases. A cross-sectional case-control study was performed with 509 women with cancer from the northern region of Portugal, including 205 healthy women and 337 women with different cervical lesions including invasive cervical. The -308G > A polymorphism genotyping was performed with TaqMan® SNP Genotyping Assay and studied for its association with cervical cancer development. This study showed increased frequency of the -308A allele in women with any cervical lesions. Statistical analysis revealed that -308A carriers are associated with an almost 2-fold increased risk for invasive cervical cancer development (p = 0.005; odds ratio (OR) = 1.87). Similar results were found when comparing the risk of progression between preinvasive lesions and invasive cervical cancer development (p = 0.002; OR = 2.41). Our results reveal that -308 TNFA AA individuals are at increased risk of invasive cervical cancer development and more important, that the risk is significantly increased for the progression from premalignant lesion to invasive cancer. Considering previous data and this study, this polymorphism confirms to be a significant marker in our population. © 2013 International Society of Oncology and BioMarkers (ISOBM). Source


Silva J.,Instituto Portugues Of Oncologia Do Porto Fg | Silva J.,University of Porto | Silva J.,Fernando Pessoa University | Cerqueira F.,Fernando Pessoa University | And 5 more authors.
Archives of Gynecology and Obstetrics | Year: 2014

Genital Chlamydia trachomatis (CT) infections have been identified as a major health problem concern. CT is associated with adverse effect on women reproduction and also associated with cervical hypertrophy and induction of squamous metaplasia, providing a possible relationship with human papillomavirus (HPV) infection. Infection by high-risk HPV types is crucial to the pathogenesis of invasive cervical cancer (ICC), but other co-variants/cofactors must be present for the development of malignancy. CT biological effect may damage the mucosal barrier, improving HPV infection, or may interfere in immune response and viral clearance supporting the persistence of HPV infection. Moreover, CT-related chronic cervical inflammation, decrease of lower genital tract antigen-presenting cells, inhibition of cell-mediated immunity, and anti-apoptotic capacity may influence the natural history of HPV infection, namely persistence progression or resolution. Although several epidemiological studies have stated a positive association involving CT and HPV-related cervical neoplastic lesions and/or cervical cancer (CC), the specific role of this bacterium in the pathogenesis of cervical neoplasia has not been completely clarified. The present review summarizes several studies on CT role in cervical cancer and suggests future research directions on HPV and CT interaction. © 2013 Springer-Verlag. Source


Sousa H.,Instituto Portugues Of Oncologia Do Porto Fg | Sousa H.,Portuguese Institute of Oncology of Porto | Sousa H.,University of Porto | Breda E.,Portuguese Institute of Oncology of Porto | And 8 more authors.
DNA and Cell Biology | Year: 2011

The tumor necrosis factor-alpha (TNF-α) is a strong proinflammatory cytokine produced by the activated macrophages in the immune response to viral infections. A common polymorphism on the promoter region of TNFA gene (-308G>A) has been associated with different susceptibilities to the development of several diseases including viral-associated neoplasias. Data suggest that the A allele has been associated with higher levels of TNF-α and, therefore, leads to increased risk of cancer development. We have performed a case-control study considering the role of the-308G>A polymorphism in 750 individuals from the northern region of Portugal, including 123 patients with nasopharyngeal carcinoma (NPC) and 627 healthy individuals. Our study revealed an increased frequency of the-308A TNFA allele in patients with NPC. The statistical analysis for recessive model revealed that-308AA genotype is associated with increased risk for the development of NPC (odds ratio=2.46; 95% confidence interval, 0.98-6.17; p=0.047); moreover, this effect was stronger in undifferentiated types, which are virtually 100% caused by the Epstein-Barr virus (odds ratio=2.75; 95% confidence interval, 1.09-6.90; p=0.025). These results reveal that in our population-308 TNFA AA genotype can represent a risk marker for NPC development and contributes for the definition of genetic susceptibility profiles for individuals at risk of development of a viral infection and associated neoplasia. © Copyright 2011, Mary Ann Liebert, Inc. Source


Sousa H.,Instituto Portugues Of Oncologia Do Porto Fg | Santos A.M.,Instituto Portugues Of Oncologia Do Porto Fg | Catarino R.,Instituto Portugues Of Oncologia Do Porto Fg | Pinto D.,Instituto Portugues Of Oncologia Do Porto Fg | And 5 more authors.
Molecular Biology Reports | Year: 2012

Human Papillomavirus infection is considered as the main etiological factor of cervical cancer (ICC), although, the role of host genetic factors in ICC susceptibility has been increasing. Immunological response is crucial for the prevention of viral associated diseases. Interleukin 1 receptor antagonist (IL-1RN) is considered to be an important regulator of host immunity and several studies have shown a potential role of a 86 bp VNTR polymorphism within intron 2 of the IL-1RN gene in host immune response variability. We investigated the role of this polymorphism in cervical cancer development in Portugal with a case-control study developed with peripheral blood samples from 196 healthy women and 340 women with cervical lesions from the Northern Region of Portugal. We observed that IL-1RN Allele 2 homozygosis was significantly higher in cases than in controls. In fact, IL-1RN A2*A2 homozygous revealed to be associated with an increased risk of HSIL + ICC (OR = 1.90; 95 % IC 1.13-3.21; p = 0.015). Furthermore, we also observed that median age of onset of HSIL + ICC was significantly different (46.0 vs 52.0) in IL-1RN A2*A2 homozygous comparing to non-A2*A2 (p = 0.028). Our results indicated that IL-1RN A2 allele is associated with an increased susceptibility to cervical cancer development, probably by increasing predisposition to shorter immune responses. © 2012 Springer Science+Business Media Dordrecht. Source


Sousa H.,Instituto Portugues Of Oncologia Do Porto Fg
Molecular biology reports | Year: 2012

Human Papillomavirus infection is considered as the main etiological factor of cervical cancer (ICC), although, the role of host genetic factors in ICC susceptibility has been increasing. Immunological response is crucial for the prevention of viral associated diseases. Interleukin 1 receptor antagonist (IL-1RN) is considered to be an important regulator of host immunity and several studies have shown a potential role of a 86 bp VNTR polymorphism within intron 2 of the IL-1RN gene in host immune response variability. We investigated the role of this polymorphism in cervical cancer development in Portugal with a case-control study developed with peripheral blood samples from 196 healthy women and 340 women with cervical lesions from the Northern Region of Portugal. We observed that IL-1RN Allele 2 homozygosis was significantly higher in cases than in controls. In fact, IL-1RN A2*A2 homozygous revealed to be associated with an increased risk of HSIL + ICC (OR = 1.90; 95 % IC 1.13-3.21; p = 0.015). Furthermore, we also observed that median age of onset of HSIL + ICC was significantly different (46.0 vs 52.0) in IL-1RN A2*A2 homozygous comparing to non-A2*A2 (p = 0.028). Our results indicated that IL-1RN A2 allele is associated with an increased susceptibility to cervical cancer development, probably by increasing predisposition to shorter immune responses. Source

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