Double-edged sword of inflammasome genetics in colorectal cancer prognosis.

Inflammation is a colorectal cancer (CRC) hallmark. Inflammasome-dependent cytokines IL-1ß and IL-18 can play a beneficial or detrimental role in tumorigenesis depending on cancer type. Variants in inflammasome genes were associated with tumor development and/or outcome, and have been proposed as potential biomarkers for population screening. In this study, 215 CRC patients followed-up for 10 years were examined for 9 polymorphisms in selected inflammasome genes. Multivariate association analysis and survival analysis were performed to evaluate the association between the polymorphisms and CRC prognosis. Variants associated with lower levels of IL-18 (rs1834481, rs5744256), or with increased activation of inflammasome receptors NLRP1 (rs12150220) and NLRP3 (rs35829419) resulted detrimental to CRC prognosis and may be used as prognostic markers.

Identification of mutations in the pah gene in pku patients in the state of mato grosso / Identificação de mutações no gene da pah em pacientes com fenilcetonúria do estado de mato grosso

ABSTRACT Objective: To identify phenylalanine hydroxylase (PAH) mutations in patients with phenylketonuria (PKU) from the Newborn Screening Service in Mato Grosso, Midwest Brazil. Methods: This is a cross-sectional descriptive study. The sample consisted of 19 PKU patients diagnosed by newborn screening. Molecular analysis: DNA extraction using the "salting-out" method. Detection of IVS10nt-11G>A, V388M, R261Q, R261X, R252W, and R408W mutations by the restriction fragment length polymorphism (RFLP) technique. Results: Two mutant alleles were identified in four patients (21.1%), one allele in five patients (26.2%), and none in the remaining ten patients (52.6%). A total of 13/38 alleles were detected, corresponding to 34.2% of the PAH alleles present. The most prevalent variant was V388M (13.2% of the alleles), followed by R261Q (10.1%) and IVS10nt-11G>A (7.9%). Three variants (R261X, R252W, and R408W) were not found. The most frequent mutation types were: missense mutation in eight alleles (18.4%) and splicing in four alleles (10.5%). The model proposed by Guldberg to determine a genotype/phenotype correlation was applied to four classical PKU patients with two identified mutations. In three of them, the predicted moderate/moderate or moderate PKU phenotype did not coincide with the actual diagnosis. The prediction coincided with the diagnosis of one classic PKU patient. The estimated incidence of PKU for Mato Grosso, Brazil, was 1:33,342 live births from 2003 to 2015. Conclusion: The only mutations found in the analyzed samples were the IVS10nt-11G>A, V388M, and R261Q. The genotype/phenotype correlation only occurred in four (5.3%) patients.

RESUMO Objetivo: Identificar mutações da fenilalanina hidroxilase (PAH) em pacientes com PKU (fenilcetonúria) do Serviço de Triagem Neonatal em Mato Grosso. Métodos: Estudo de corte transversal. Amostra composta de 19 pacientes com PKU através do exame de triagem neonatal biológica. Análise molecular: a) extração de DNA pela metodologia "salting out". B) detecção de mutações IVS10nt-11G>A, V388M, R261Q, R261X, R252W e R408W pela técnica de polimorfismo de comprimento de fragmento de restrição (RFLP). Resultados: Dois alelos foram identificados em quatro pacientes (21,1%), um alelo em cinco pacientes (26,2%) e nenhum nos dez pacientes restantes (52,6%). Um total de 13/38 alelos foram identificados, correspondendo a 34,2% dos alelos PAH presentes. A variante mais prevalente foi a V388M (13,2% dos alelos), seguida de R261Q (10,1%) e IVS10nt-11G>A (7,9%). Três variantes (R261X, R252W e R408W) não foram encontradas. Os tipos de mutações mais frequentes foram: troca de sentido em oito alelos (18,4%) e emenda em quatro alelos (10,5%). O modelo proposto por Guldberg para determinar uma correlação genótipo/fenótipo foi aplicado para quatro pacientes clássicos de PKU, com duas mutações identificadas. Em três, o fenótipo previsto de PKU moderada/moderada ou moderada não coincidiu com o diagnóstico real. A predição coincidiu com o diagnóstico de um paciente PKU clássico. A incidência de PKU estimada para Mato Grosso, Brasil foi de 1:33.342 nascidos vivos para o período de 2003 a 2015. Conclusões: Foram encontradas apenas as mutações IVS10nt-11G>A, V388M, R261Q nas amostras analisadas. A correlação genótipo/fenótipo ocorreu em quatro (5,3%) pacientes.

EPIDEMIOLOGICAL ANALYSIS AND INVESTIGATION OF +114G/T POLYMORPHISM IN THE GENE IL-2 IN PATIENTS WITH BREAST CANCER IN THE STATE OF MATO GROSSO / Análise epidemiológica e investigação do polimorfismo +114G/T no gene IL-2 em pacientes com câncer de mama no estado de Mato Grosso

Objective: This study aimed to determine the relationship between the rs2069763 polymorphism of the Interleukin-2 (IL-2) gene and the development of breast cancer (BC) in women in the state of Mato Grosso. Methods: This is an observational epidemiological study of case-control based on a bank of samples with 254 patients and 243 control women. The patients were subjected to anamnesis and collection of peripheral blood after their permission. The collecting of peripheral blood was carried out and was used for DNA extraction, followed by a genotyping process by Polymerase Chain Reaction-Restriction Fragment Length Polymorfism (PCR-RFLP) and polyacrylamide gel electrophoresis 8%. Results: The frequency of genotypes between cases and controls was 19.5% for the TT genotype; 44.2% and 32.1% for TG and GG, respectively. It was found, in samples of patients, a frequency of 14.9% for the TT genotype, 77.2% and 31.8% for TG and GG, respectively. In the controls, it was observed frequency of 24.1% for the TT genotype, 41.5% and 30.4% for TG and GG, respectively. Conclusions: The present study showed a higher incidence of polymorphism +114G/T in the control sample, suggesting a protective effect for the BC in the sample of women from Mato Grosso.

Objetivo: O presente estudo teve como objetivo verificar a relação existente entre o polimorfismo rs2069763 do gene interleucina-2 (IL-2) e o desenvolvimento do câncer de mama (CM) em mulheres do estado de Mato Grosso. Métodos: Trata-se de um estudo epidemiológico observacional do tipo caso controle tendo como base um banco de amostras com 254 pacientes casos e 243 mulheres controles. As pacientes foram submetidas à anamnese e à coleta de sangue periférico após terem autorizado os procedimentos. Procedeu-se a coleta de sangue periférico e este foi utilizado para a extração do DNA, seguido pelo processo de genotipagem por meio da técnica de Polymerase Chain Reaction-Restriction Fragment Length Polymorfism (PCR-RFLP ­ Reação em Cadeia da Polimerase-Polimorfismo no Comprimento de Fragmentos de Restrição) e eletroforese em gel de poliacrilamida 8%. Resultados: A frequência dos genótipos, entre casos e controles, foi de 19,5% para o genótipo TT; 44,2% para TG e 32,1% para GG. Encontrou-se, nas amostras de pacientes, uma frequência de 14,9% para o genótipo TT, 77,2% para TG e 31,8% para GG. Nos controles observou-se uma frequência de 24,1% para o genótipo TT, 41,5% para TG e 30,4% para GG. Conclusões: O presente estudo demonstrou maior incidência do polimorfismo +114G/T na amostra controle, sugerindo um efeito protetor para o CM na amostra de mulheres de Mato Grosso.

Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients.

AIM: To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC). METHODS: A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A -1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C>T polymorphism in 129 patients and for VEGF-A -634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS: In the univariate analysis there was a significant association (OR = 0.32; P = 0.048) between genotype CC of the VEGF-A -1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A -1498C>T polymorphism and VEGF-A -634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A -1498C>T polymorphism was significantly correlated with the 5-year survival (P = 0.032), but not significant difference (P = 0.27) was obtained with the VEGF-A -634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT (HR = 2.79) and CC (HR = 4.67) of the polymorphism VEGF-A -1498C>T and the genotype CC (HR = 3.76) of the polymorphism VEGF-A -634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION: The CT and CC genotypes of the VEGF-A -1498C>T and the CC genotype of the VEGF-A -634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.

Investigação do polimorfismo C3435T no gene MDR1 e sua associação com o câncer de mama em mulheres de Mato Grosso, Brasil / Investigation of the C3435T polymorphism in the MDR1 gene and itsassociation with breast cancer in women of Mato Grosso, Brazil

Objetivo: Investigar a frequência do polimorfismo C3435T no gene MDR1 e sua associação com câncer de mama (CM) em mulheres de MT. Método: O estudo tem desenho epidemioló- gico descritivo e observacional do tipo caso-controle. Analisou-se o genótipo do polimorfismo C3435T no gene MDR1 a partir de sangue periférico; foram comparadas 201 pacientes com 177 controles. As pacientes foram mulheres portadoras de CM, as controles foram mulheres não portadoras de CM comprovado por exame clínico e mamografia. Os dados foram coletados por meio de entrevista com as mulheres, coleta de sangue para genotipagem e coleta de dados de prontuários médicos das pacientes. O projeto teve aprovação do Comitê de Ética em Pesquisa. Resultados: O polimorfismo C3435T no gene MDR1 teve distribuição semelhante entre as pacientes e as controles, sem diferença estatisticamente significativa entre as amostras. Conclusões: A frequência do polimorfismo C3435T do gene MDR1 é semelhante à encontrada na literatura. Não foi encontrada diferença estatisticamente significativa na frequência dos genótipos do polimorfismo C3435T no gene MDR1 entre as pacientes com CM e as controles. O polimorfismo também não apresentou associação com fatores prognósticos para o CM.

Objective: To investigate the frequency of the C3435T polymorphism in the MDR1 gene and its association with breast cancer (BC) in women of MT. Method: The study is descriptive and observational epidemiological case-control design. We analyzed the genotype of the C3435T polymorphism in the MDR1 gene in peripheral blood were compared in 201 patients with 177 controls. Patients were women with breast cancer, the controls were not women with BC confirmed by clinical examination and mammography. Data were collected through interviews with women, blood was collected for genotyping and data collection from medical records of patients. The project was approved by the Research Ethics Committee. Results: The C3435T polymorphism in the MDR1 gene had similar distribution between patients and controls with no statistically significant difference between samples. Conclusions: The frequency of C3435T polymorphism of MDR1 gene is similar to that found in the literature. We found no statistically significant difference in genotype frequency of C3435T polymorphism in the MDR1 gene among patients with BC and controls. The polymorphism also showed no association with prognosis for BC factors.

Características clínicas e citogenéticas da síndrome de Turner na região Centro-Oeste do Brasil / Clinical and cytogenetic aspects of the Turner syndrome in the Brazilian Western region

OBJETIVO: examinar a associação entre características citogenéticas e alterações clínicas em pacientes com síndrome de Turner (ST). MÉTODOS: Foram incluídas 42 pacientes. Os dados clínicos foram colhidos e registrados em formulário padronizado com entrevista do responsável e, quando possível, com a própria paciente, seguido de exame físico detalhado. A associação entre cariótipo e intercorrências clínicas foram examinadas pelo teste do χ2. RESULTADOS: Das pacientes, 64 por cento tinham cariótipo 45,X; 26,2 por cento 45,X/46,X; 7 por cento 45,X/46Xi(Xq) e 2,3 por cento 45,X/46,X,Del(Xq). Independentemente do cariótipo, 100 por cento das pacientes apresentaram baixa estatura. A implantação baixa dos cabelos foi mais frequente nas pacientes com cariótipo 45,X (p=0,03). Anomalias cardiovasculares (45 por cento), otites (43 por cento), disfunção da tireoide (33 por cento) e hipertensão arterial (26,6 por cento) foram as alterações clínicas mais frequentes e não mostraram correlação com o cariótipo. A avaliação de medidas antropométricas revelou correlação positiva entre a idade e o diâmetro da cintura e quadril (r=0,9; p=0,01). Trinta e uma pacientes (74 por cento) faziam ou tinham feito uso de medicamentos, sendo que hormônio de crescimento (43 por cento), esteroides sexuais (30 por cento), tiroxina (11,9 por cento) e oxandrolona (9,5 por cento) foram os mais utilizados. A comparação da idade da gestação no momento em que ocorreu o parto com dificuldade no aprendizado mostrou razão de prevalência de 1,71 (p>0,05). CONCLUSÃO: a implantação baixa dos cabelos é o estigma mais prevalente nas pacientes com cariótipo 45,X e as alterações clínicas mais comuns são as cardiovasculares, otites, hipertensão arterial e disfunções tireoidianas, porém não apresentam correlação com o cariótipo.

PURPOSE: to examine the association between cytogenetic characteristics and clinical and epidemiological changes in patients with Turner syndrome (TS). METHODS: Forty-two patients were included. Data were collected using a standardized questionnaire in interviews conducted with the responsible person and, when possible, with the patient. A detailed physical examination was performed. The association between karyotype, stigmata and clinical disorders were examined using the χ2 test. RESULTS: Sixty-four percent of TS patients were 45,X; 26,2 percent 45,X/46,X;7 percent 45,X/46Xi(Xq), and 2,3 percent 45,X/46,X,Del(Xq). Regardless of the karyotype, all patients had short stature. Low hair implantation was more frequent in patients with 45,X (p=0.03). Cardiovascular abnormalities (45 percent), otitis (43 percent), thyroid dysfunction (33 percent) and hypertension (26.6 percent) were the most frequent clinical disorders, but without correlation with the karyotype. Anthropometric measurements revealed a positive linear correlation of waist and hip circumference with age (r=0.9, p=0.01). Thirty-one patients (74 percent) were using or had previously used growth hormone (43 percent), sex steroids (30 percent), thyroxine (11.9 percent) or oxandrolone (9.5 percent). Comparison between gestational age at birth and learning difficulties showed a prevalence ratio of 1.71 (p>0.05). CONCLUSION: Low hair implantation is the most prevalent stigma in patients with a 45,X karyotype and the most common clinical changes were cardiovascular problems, otitis, thyroid dysfunction and hypertension; however, they did not show any correlation with the karyotype.

Vigilância epidemiológica de anomalias congênitas em um hospital universitário de Mato Grosso, Brasil / Surveillance of congenital anomalies in an university hospital of Mato Grosso, Brazil

Objetivos: Sistematizar o registro de Anomalias Congênitas (AC) em um Hospital Universitário de Mato Grosso e avaliar a qualidade do preenchimento do Campo 34 da Declaração de Nascidos Vivos (DVN). Método: Estudo prospectivo no qual foram avaliados, entre dezembro de 2005 e novembro de 2006, os recém-nascidos vivos (RNs) vivos do Hospital Geral Universitário visando identificar AC. Foram estabelecidas as frequências de AC na amostra e de outras variáveis. A adequação do preenchimento do Campo 34 da DNV foi estudada. Resultados: Foram 2.750 RNs, sendo 63 com AC (2,29%). Aproximadamente 80% dos RNs pesavam entre 2501 e 4000g. Os grupos de maior risco para AC foram os de 1501-2000 (7,46%) e de 1001-1500 gramas (5,17%); mães na faixa etária de 40-44 anos, seguida de 35-39 e 30-34 anos. Aproximadamente 85% das mães eram tercigestas. Observou-se maior frequência de AC entre as mulheres de 6 e 7 gestações. Nos RNs com AC, constatou-se que 30 eram do sexo masculino, 32, do sexo feminino e apenas 1 caso de intersexo. Agrupando: Anomalias de membros (16), anomalias do sistema nervoso (10), anomalias orofaciais (9), anomalia genital (6), defeitos de parede abdominal (5), síndrome de Down (3), anomalias do sistema respiratório (3), acondroplasia (1), anomalias múltiplas (4) anomalias não agrupadas (6). Em 23 casos, o preenchimento do Campo 34 foi feito de maneira correta. No restante (63,49%), o preenchimento foi incorreto ou não existente. Conclusão: Há subregistro de AC no Hospital estudado. O preenchimento do Campo 34 tem sido sistematicamente negligenciado, acarretando prejuízos nos registros oficiais.

To systematise the record of Congenital anomalies (CA) in a University Hospital of Mato Grosso and assess the quality of the completion of the Field 34 of Declaration of Live Births (DLB). Methods: Prospective which were evaluated between December 2005 and November 2006 the University General Hospital of living newborn (LN) to identify CA. Have been established in the frequencies of CA sample and other variables. The adequacy of the completion of Field 34 of DLB was studied. Results: There were 2,750 LN, 63 with CA (2.29%). Approximately 80% of LN weighs between 2501 and 4000g. The groups most at risk for CA were those of 1501-2000 (7.46%) and 1001-1500grams (5.17%); mothers in the age group of 40-44 years, followed by 35-39 and 30-34 years old. Approximately 85% of mothers had 3 pregnancies. Increased frequency of CA was observed between women, 6 and 7 pregnancies. In LN with CA, it was found that 30 were male, 32 female and only 1 intersex. Combining: Anomalies of members (16), disorders of the nervous system (10), abnormal orofacial (9), genital anomaly (6), defects in the abdominal wall (5), Down syndrome (3), disorders of the respiratory system (3), achondroplasia (1), multiple anomalies (4) anomalies not grouped (6). In 23 cases, the completion of the Field 34 has been done so correctly. In the remainder (63.49%), the filling was incorrect or non-existent. Conclusion: There a few registration of CA in Hospital studied. The completion of the Field 34 has been systematically neglected, resulting in losses official records.

Estudo descritivo da demanda de um Serviço de Citogenética Clínica no Estado do Mato Grosso: 2003 a 2007 / Study describing the demand for a service Cytogenetics Clinics in Mato Grosso: 2003 to 2007

Objetivo: Identificar a frequência dos resultados citogenéticos realizados na demanda da Unidade de Genética Médica e Biologia Molecular do Hospital Geral Universitário (UGM/UNIC) entre 2003 e 2007. Método: Estudo retrospectivo de pacientes encaminhados a UGM/UNIC provenientes dos ambulatórios do HGU e de outros serviços de saúde do Estado e região...

Objective: To evaluate the results achieved cytogenetic demand in the Unit of Medical Genetics and Molecular Biology of the University General Hospital (UGM/UNIC) between 2003 and 2007. Methods: Retrospective study patients referred to HGU/UNIC from the state and region...