Association between polymorphisms in the genes encoding toll-like receptors and dectin-1 and susceptibility to invasive aspergillosis: a systematic review

Abstract Invasive aspergillosis is a common fungal infection in immunocompromised individuals. Some studies have shown that toll-like receptor and dectin-1 genetic polymorphisms may alter signaling pathways, thus increasing an individual's susceptibility to invasive aspergillosis. We investigated the pertinent literature to determine whether polymorphisms in the genes encoding toll-like receptors and dectin-1 increase the susceptibility to invasive aspergillosis. This study systematically reviewed the literature using the databases PubMed/PMC, Scopus, and Web of Science using the keywords invasive aspergillosis, polymorphism, Toll-like, and Dectin-1. From the initial search, 415 studies were found and according to our inclusion and exclusion criteria, eight studies were selected. Several studies described single-nucleotide polymorphisms (SNPs) that are associated with a greater susceptibility to invasive aspergillosis. These SNPs were found in the genes that encode toll-like receptors 1, 3, 4, and 5 and the gene that encodes dectin-1; upon activation, both cellular receptors initiate a signaling cascade that can result in the production of cytokines and chemokines. Thus, our literature review uncovered a significant association between polymorphisms in the genes that encode toll-like receptors and dectin-1 and invasive aspergillosis. More studies should be performed to better understand the relationship between toll-like receptor and dectin-1 genetic polymorphisms and invasive aspergillosis susceptibility.

Padrão de metástase no câncer de mama triplo negativo / Metastatic pattern of triple negative breast cancer

Introdução: Os carcinomas de mama triplo negativos (TN) são neoplasias malignas clinicamente heterogêneas que não apresentam receptores para estrógeno, progesterona e superexpressão do HER2 (ERBB2 ou NEU). Os TN estão entre os subtipos mais agressivos e mortais de câncer de mama. Objetivo: O presente estudo objetivou elucidar o comportamento metastático dos carcinomas de mama TN e correlacioná-los a idade, histologia, grau de diferenciação, tamanho do tumor, entre outras variáveis clínico-patológicas. Métodos: Foram selecionados 140 prontuários de pacientes com câncer de mama no Hospital Araújo Jorge em Goiânia (GO) durante o período de 1998 a 2010, dos quais 75 casos (53,6%) possuíam diagnóstico de câncer de mama TN. Resultados: As variáveis que apresentaram significância foram o tamanho do tumor (p=0,0497) e o número de linfonodos acometidos (p=0,002). Durante os cinco anos de observação, a doença metastática ocorreu em pouco mais da metade de todas as pacientes (52,0%). Os locais mais comuns de recorrência foram pulmão, osso e cérebro. Conclusão: Os resultados indicam que as pacientes com carcinomas mamários TN apresentam um perfil tumoral mais agressivo, necessitando de maior vigilância nos anos iniciais do seguimento.

Introduction: Triple negative breast cancers (TNBC) are clinically heterogeneous malignancies that do not present receptors of the estrogen, progesterone and HER2 (ERBB2 or NEU). TNBC are among the most aggressive and deadly breast cancer subtypes. Objective: The present study aimed to elucidate the metastatic pattern of TNBC and attempt to correlate it to age, histology, tumor grade, tumor size, and other clinicopathological variables. Methods: 140 clinical files of patients with breast cancer in Araújo Jorge Hospital in Goiânia (GO), during the period 1998-2010, were selected; among these, 75 cases (53.6%) with TNBC diagnosis were found. Results: The significant variables were tumor size (p=0.0497) and number of metastatic lymph nodes (p=0.002). During the period of five years of observation, metastatic disease occurred in over half of all patients (52.0%). The most common sites of recurrence were lung, bone, and brain. Conclusion: Our finds concluded that patients with TNBC feature a more aggressive type of tumor, requiring increased vigilance in the early years of follow-up

Polimorfismo nulo do gene GSTM1 na suscetibilidade do câncer de mama:evidências baseadas em meta-análise / Null polymorphism of GSTM1 gene in susceptibility of breast cancer: evidence based on meta-analysis

Introdução: O câncer de mama é a segunda neoplasia mais frequente no mundo e a primeira mais comum no sexo feminino. Dados epidemiológicos apontam o efeito de agentes carcinogênicos e fatores ambientais para maior susceptibilidade em desenvolver o câncer de mama. No contexto das avaliações moleculares, o polimorfismo nulo do gene GSTM1 é comumente estudado na tentativa de associá-lo ao desenvolvimento desta neoplasia. Objetivo: Avaliar se os indivíduos que apresentam o polimorfismo nulo para o gene GSTM1 possuem susceptibilidade ao câncer de mama. Métodos: Realizou-se meta-análise com 10 estudos do tipo caso-controle, que apresentavam pacientes com confirmação histológica de câncer de mama e que faziam uso da PCR e/ou sequenciamento de DNA para determinar o polimorfismo nulo do gene GSTM1. A análise foi realizada após a coleta dos dados necessários (autor, ano de publicação, país e resultados). Os cálculos estatísticos e a representação dos dados foram obtidos com o auxílio do software BioEstat® 5.0. Resultados: O total de indivíduos, após o agrupamento dos dados dos estudos, foi de 7.607 (3.759 casos e 3.848 controles). As frequências para o polimorfismo nulo do gene GSTM1 em pacientes com câncer de mama foram, respectivamente, 51,0% no grupo casos e 50,3% no grupo controle. A análise dos dados obtidos revelou OR: 0,967 e IC95% 0,883?1,060. Conclusão: Conforme os dados obtidos na meta-análise, não foi encontrada associação significativa entre o polimorfismo nulo do gene GSTM1 e o desenvolvimento do câncer de mama. Assim, os resultados do presente estudo mostram que o polimorfismo em questão não alterou suscetibilidade ao câncer de mama, portanto, devem-se levar em consideração outros fatores com maior significância, como: tabagismo, outros marcadores genéticos, tais como BRCA1 e BRCA2, paridade, entre outros.

Introduction: Breast cancer is the second most common cancer worldwide and the first more common in females. Epidemiological data show the effect of carcinogens and environmental factors in the increased susceptibility of developing breast cancer. In the context of molecular assessments, the null polymorphism of GSTM1 gene is commonly studied in an attempt to associate with the development of this neoplasm. Objective: To evaluate whether individuals with the GSTM1-null polymorphism possess susceptibility to breast cancer. Methods: It was conducted a meta-analysis of 10 case-control studies, which had patients with histological confirmed breast cancer and used PCR and/or DNA sequencing to determine the null polymorphism of GSTM1 gene. The analysis was performed after gathering the necessary data (author, publication year, country and results). Statistical calculations and the representation of the data were obtained with the help of BioEstat® 5.0 software. Results: The total number of individuals, after grouping the data was 7,607 (3,759 cases and 3,848 controls). The frequencies for the null polymorphism of GSTM1 gene were, respectively, 51.0% in the case group and 50.3% in the control group. The analysis of the obtained data revealed OR: 0.967 and 95%CI 0.883?1.060. Conclusion: According to the data obtained by meta-analysis it was not found significant association between GSTM1-null polymorphism and the development of breast cancer. Thus, the results of this study revealed that the polymorphism in question did not change the susceptibility to breast cancer, so it should be considered other factors with greater significance, such as smoking, other genetic markers like BRCA1 and BRCA2, parity, among others.