RESUMO
BACKGROUND: Metallothioneins (MTs) gene polymorphisms have been associated with the ability of free radical scavenging and detoxification of heavy metals leading to cancer development. Our aim was to revisit, in a Brazilian population, single-nucleotide polymorphisms (SNPs) of the MT gene family previously associated with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: A case-control investigation with 28 OSCC patients and 45 controls was conducted, using conventional risk factors (tobacco use and alcohol consumption) as covariates. SNPs genotyping for rs8052334 (MT1B), rs964372 (MT1B), and rs1610216 (MT2A) was performed by PCR-RFLP, and SNPs for rs11076161 (MT1A) were analyzed by TaqMan assay. RESULTS: The only SNP associated with increased risk for OSCC was the MT-1A AA genotype (OR = 4.7; p = 0.01). We have also evidenced for the first time a significant linkage disequilibrium between the SNPs of MT-2A and MT-1A in this population with the highest frequency (30%) of the unfavorable haplotype G/A/C/T (rs1610216 / rs11076161 / rs964372 / rs8052334) of MT gene polymorphisms (OR = 6.2; p = 0.04). Interestingly, after removing the effects of conventional risk factors, we have uncovered the significance of the AA genotype of the rs11076161 with increased odds of 19-fold higher towards OSCC development. CONCLUSIONS: This is the first demonstration that a significant linkage disequilibrium among gene polymorphisms of the MT family may affect susceptibility to oral cancer, which is conditioned by the G/A/C/T haplotype (rs1610216/rs11076161/rs964372/ rs8052334) and the MT-1A gene polymorphism has a potential clinical utility for the OSCC risk assessment.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Brasil , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Metalotioneína/genética , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
We assess the prevalence of human papillomavirus (HPV) and cofactors for cervical severe disease, as contribution for vaccine strategies at the right moment in which Brazilian health authorities have approved an anti-HPV vaccine. A case-control study was undertaken with 201 women who attended a public health service with previous abnormal cytology. The HPV status was ascertained by consensus primers My09/11 and typed by 6, 11, 16, 18, 31, 33, 35, and 58 specific primers. Patients diagnosed with high-grade squamous intraepithelial lesions (HSIL) and cervical cancer were referred as cases (n = 84). Patients with normal/inflammatory cervix or carrying benign cervical lesions were included in controls (n = 117). The overall prevalence of HPV infection was 75.6%, with 91.7% among cases. In spite of HPV 16 being the most frequent type (53.3%), 27.6% of infections were attributed to nonvaccine types. High-risk HPV were strongly associated to older women (OR = 6.7). Otherwise, age at the first intercourse (OR = 7.10), three or more parities (OR = 3.05), abortion episodes (OR = 4.80), and smoking (OR = 3.83) conferred a heavy effect in younger women. Among mediators affecting the progress from HSIL to cancer, age played the main role in easing the progression (OR = 1.09, P = 0.002) followed by education level (OR = 4.20, P = 0.066). White ethnia showed to be a protective factor (OR = 0.32, P = 0.055). Predictors from HPV exposure to malignant disease include demographic and behavioral factors. Public policies such as improvement of education and continued prevention campaigns might contribute to reduce this picture. This work also gives background, in identifying a target population, for implementing future vaccine strategies.
Assuntos
Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Prevalência , Prognóstico , Fatores de Risco , Comportamento Sexual , Classe Social , Neoplasias do Colo do Útero/etiologia , Displasia do Colo do Útero/etiologiaRESUMO
Two homogeneous sulfated polysaccharides obtained from the red seaweeds Gymnogongrus griffithsiae and Cryptonemia crenulata, the kappa/iota/nu carrageenan G3d and the dl-galactan hybrid C2S-3, were assayed for their antiviral properties against the four serotypes of dengue virus (DENV) in different host cell types. Both seaweed derivatives were selective inhibitors of DENV-2 multiplication in Vero cells with inhibitory concentration 50% (IC50) values around 1 microg/ml and selectivity indices > 1000. The compounds had a lower antiviral effect against DENV-3 (IC50 values in the range 13.9-14.2 microg/ml), an even lower effect against DENV-4 (IC50 values in the range 29.3 to > 50 microg/ml) and were totally inactive against DENV-1. With respect to the host cell, the polysulfates were inhibitors of DENV-2 and DENV-3 in the human hepatoma HepG2 and foreskin PH cells, with similar antiviral effectiveness as in Vero cells, but were totally inactive in mosquito C6/36 HT cells. Mechanistic studies demonstrated that G3d and C2S-3 were active DENV-2 inhibitors only when added together with the virus or early after infection, and both initial processes of virus adsorption and internalization are the main targets of these compounds. Therefore, the variations in antiviral activity of the polysaccharides depending on the viral serotype and the host cell may be ascribed to differences in the virus-cell interaction leading to virus entry.