APOBEC3A/B Polymorphism Is Not Associated with Human Papillomavirus Infection and Cervical Carcinogenesis.

The persistence of a high-risk Human papillomavirus (HPV-HR) infection of the cervix results in different manifestations of lesions depending on the immunologic capacity of the host. Variations in apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC)-like genes, such as the APOBEC3A/B deletion hybrid polymorphism (A3A/B), may contribute to cervical malignancy in the presence of HPV. The aim of this study was to investigate the association between the A3A/B polymorphism and HPV infection and the development of cervical intraepithelial lesions and cervical cancer in Brazilian women. The study enrolled 369 women, who were categorized according to the presence of infection and subdivided according to the degree of intraepithelial lesion and cervical cancer. APOBEC3A/B was genotyped by allele-specific polymerase chain reaction (PCR). As for the A3A/B polymorphism, the distribution of genotypes was similar between groups and among the analyzed subgroups. There were no significant differences in the presence of infection or development of lesions, even after exclusion of confounding factors. This is the first study to show that the A3A/B polymorphism is not associated with HPV infection and the development of intraepithelial lesions and cervical cancer in Brazilian women.

CXCL12/CXCR4 axis gene variants contribute to an increased vulnerability to HPV infection and cervical oncogenesis.

PURPOSE: Every year, more than half a million women are diagnosed with cervical cancer (CC). Individual factors may contribute to the cervical cancer development, such as immunogenetic variation. CXCL12/CXCR4 axis is involved in tumor progression and aggressiveness. In the present study, we aimed to investigate a possible association between two single-nucleotide variants (CXCL12 rs1801157 and CXCR4 rs2228014) with HPV infection and cervical cancer development. METHODS: PCR technique was used to test HPV positivity in 424 women, in which the allelic frequency of CXCL12 rs1801157 and CXCR4 rs2228014 was also assessed by PCR-restriction fragment length polymorphism. RESULTS: CXCL12 rs1801157 was associated with HPV infection in the allelic distribution as well in the codominant, dominant and recessive genetic models; as well with squamous intraepithelial lesions (SIL) and CC in the codominant and dominant models. CXCR4 rs2228014 was associated to HPV infection in the codominant model and allelic distribution; as well with SIL/CC in the codominant, dominant and allelic models. Independent associations were found for CXCL12 AA genotype and HPV infection, SIL and CC development, as well as, CXCR4 allele T and HPV infection and CC. The variants interaction analysis demonstrated that the presence of both polymorphisms increases the susceptibility of HPV infection in 10.1 times, SIL (2 times) and CC development in 4.2 times. CONCLUSIONS: This is the first study demonstrating that the interaction of CXCL12 and CXCR4 variants contributes to the increased susceptibility of HPV infection, squamous intraepithelial lesions and cervical cancer development.

Development of cervical intraepithelial lesions and cervical cancer is not influenced by SOD2 RS4880 polymorhism.

Some of the more than 200 known HPV types are essential for cervical cancer development, the third type of cancer most incident in the female population. However, for the malignant transformation occur, some cofactors are needed, as the reactive oxygen species (ROS), which can be neutralized by the antioxidant system. The SOD2 enzyme, encoded by the same name gene, is found in mitochondria and is part of the first line of defense against oxidative stress damage. Genetic polymorphisms can act by altering the efficiency of the enzyme, among which the most studied is the rs4880. Thus, the purpose of the present study was to evaluate the association of this polymorphism with HPV infection and the development of low and high grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer, in 407 women attended by the public health system in Brazil. HPV detection in cervical secretion samples was carried out by polymerase chain reaction (PCR) and blood samples were used for polymorphism genotyping through PCR followed by restriction fragment length polymorphism (RFLP). PCR and restriction products were subjected to 10% polyacrylamide gel electrophoresis. HPV negative group (control) included 158 women and the HPV positive group (case) 249 women. The infected group was divided into No Lesion (n = 90), LSIL (n = 20), HSIL (n = 67) and cervical cancer (n = 72). The data found on socio-epidemiological characteristics and habits corroborated with data found in the literature. The distribution of genotypes in the control group was 51.9% women TC, 29.8% TT and 18.3% CC. In the case group, the distribution was 55.0% women TC, 26.1% TT and 18.9% CC. This is the first study evaluating the influence of SOD2 rs4880 polymorphism on HPV infection, the development of cervical intraepithelial lesions and cervical cancer in a Brazilian population, although additional studies are needed to corroborate the results.

IL-10 c.-592C>A (rs1800872) polymorphism is associated with cervical cancer.

PURPOSE: Interleukin-10 (IL-10) is an immunoregulatory cytokine and its cervical and serum concentrations have been associated with a poor prognosis of cervical cancer. The rs1800872 polymorphism (c.-592C>A) in the promotor region of the IL-10 gene affects the production and expression of IL-10 and thus is able to determine the immune response profile in the cervix. Therefore, the aim of this work is to state the association between IL-10 c.-592C>A polymorphism and cervical cancer. METHODS: Genomic DNA was extracted from patient's peripheral blood and tumor biopsy. Socio-demographic, sexual behavior and reproductive characteristics data were collected using a questionnaire. RESULTS: Co-dominant model in logistic binary regression adjusted for confounders, showed that patients presenting with C/A genotype had 2.15 times more chances for developing cervical cancer (OR 2.15; CI95% 1.02-4.56). The dominant model, C/A + A/A, was also independently associated with 2.71 times more chances for cervical cancer development when compared to control patients (OR 2.71; CI95% 1.05-4.47). CONCLUSION: Our study analyses show the association between cervical cancer and IL-10 c.-592C>A polymorphism, demonstrating that the allele A presence was independently associated with higher risks of cervical cancer development.

Is there a role for cervicography in the detection of premalignant lesions of the uterine cervix?: a Brazilian experience.

OBJECTIVE: This study aimed to compare cervical cancer screening by cervicography with screening by Pap test. MATERIALS AND METHODS: This was a comparative multicenter study of cervical cytology and cervicography. The cervicography (slides of the cervix) was taken after the Pap test was completed. In total, samples were collected from 1176 patients. Colposcopy with biopsy was considered the gold standard for the final diagnosis of lesions observed by the Pap test and cervicography. Statistical analysis was performed using the binomial test. RESULTS: In cases in which the Pap test was negative for cervical lesions, diagnosis by cervicography was positive in 15 cases of cervical intraepithelial neoplasia 1 (CIN 1) (p = .00052), in 1 case of CIN 2, in 1 case of CIN 3, and in 1 case of cancer. However, cervicography produced 3 false-positive results (p < .0001). CONCLUSIONS: Cervicography may be used as a complementary screening method to the Pap test for cervical cancer.

Tempo decorrido entre o diagnóstico de câncer de mama e o início do tratamento, em pacientes atendidas no Instituto de Câncer de Londrina (ICL) / Waiting time between breast cancer diagnosis and the beginning of the treatment for women attending at Londrina´s Cancer Hospital (ICL)

Metodologia: Foram revisados 180 prontuários de mulheres com diagnóstico de câncer de mama entre janeiro de 2003 a outubro de 2004, com o objetivo de identificar o tempo de demora entre o diagnóstico e o início de tratamento e contribuir com maneiras de reduzir este tempo e discutir os resultados. Resultados: Das pacientes, 71 (39%) apresentaram tumor localizado (T1-T3 N0 M0); 96 pacientes tinham doença regional (N1-N3 /M0 ou T4N0M0) e 13 apresentavam doença metastática (M1). O tempo decorrido entre o primeiro método de imagem ou exame físico alterados até o início do tratamento foi superior a 90 dias na grande maioria dos casos (72%). Apenas 40% das mulheres conseguiram a primeira consulta no hospital de referência em 30 dias e mais da metade das pacientes (50,5%) demorou mais de 90 dias desde a primeira consulta no ICL até serem submetidas ao tratamento definitivo. Conclusão: A maioria das pacientes estudadas ainda leva muito tempo entre a procura do serviço primário até o encaminhamento ao serviço terciário e também há muita demora entre a entrada da paciente com suspeita de câncer de mama no serviço especializado. Os programas de rastreamento de câncer de mama têm o intuito de detectar precocemente o câncer e reduzir as taxas de mortalidade. O sistema de saúde pública necessita ter maior integração nos níveis primário, secundário e terciário.

Avaliação da expressão da proteína bcl-2 no carcinoma de mama: estudo em punção aspirativa por agulha fina; correlação com grau histológico em espécimes cirúrgicos correspondentes / Bcl-2 protein expression evaluation in breast cancer: study on fine needle aspirates; correlation with histologic grade in corresponding surgical material

INTRODUÇÄO: O gene bcl-2 codifica uma proteína envolvida no processo de controle da apoptose. Inicialmente descrito em linfomas e posteriormente em tecidos epiteliais, sua expressäo é freqüentemente encontrada em carcinomas de mama, associada a fatores de prognóstico favorável. Como a punçäo aspirativa por agulha fina (PAAF) tem sido utilizada como um método confiável na investigaçäo de carcinomas de mama, acessamos a expressäo de bcl-2 em material assim obtido e correlacionamos sua positividade com o grau histológico, avaliado em material cirúrgico correspondente, das respectivas pacientes, seguindo a classificaçäo de SBR (Scarff, Bloom e Richardson). OBJETIVOS: Avaliar a expressäo de bcl-2 em PAAF e correlacionar com grau histológico. METODOLOGIA: A positividade do bcl-2 foi analisada, por imunocitoquímica, em 118 casos consecutivos de PAAF e correlacionada com grau histológico em material cirúrgico correspondente, segundo classificaçäo de SBR. RESULTADOS: A positividade para bcl-2 foi encontrada em 77 de 118 casos de PAAF (65,25 por cento) e foi inversamente proporcional ao grau histológico (84,37 por cento, p = 0,0022). CONCLUSÄO: A expressäo de bcl-2 em PAAF correlaciona-se com fator de bom prognóstico. O índice de positividade encontrado, assim como a correlaçäo inversa com grau histológico, está de acordo com dados publicados previamente. O fácil e rápido manejo do material obtido por PAAF permite a aplicaçäo de técnicas complementares, de maneira confiável, como demonstra este estudo. A positividade do bcl-2 correlacionada com baixo grau histológico, assim como com outros fatores de bom prognóstico, pode, no futuro, proporcionar informaçäo preditiva e prognóstica para pacientes candidatas a tratamento quimioterápico neo-adjuvante