Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries

<p>Abstract</p> <p>Background</p> <p>Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome.</p> <p>Methods</p> <p>Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed.</p> <p>Results</p> <p>Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson).</p> <p>Conclusions</p> <p>The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.</p

Disponibilidade dos metais pesados tóxicos cádmio, chumbo e cromo no solo e tecido foliar da soja adubada com diferentes fontes de NPK+Zn Availability of cadmium, lead and chromium toxic heavy metals in soil and soybean leaf tissue fertilized with different sources of NPK+Zn

Os fertilizantes utilizados para suprir micronutrientes podem apresentar metais pesados tóxicos em sua composição que podem proporcionar severas consequências ao meio ambiente. Plantas cultivadas na presença de determinadas concentrações de elementos tóxicos podem oferecer risco de contaminação, pois os acumulam em seus tecidos. Desse forma, neste trabalho objetivou-se avaliar a disponibilização dos metais pesados tóxicos Cd, Pb, e Cr para o solo e tecido foliar da cultura da soja, cultivada a campo e fertilizada com um formulado N:P2O5:K2O e diferentes fontes de Zn. O delineamento experimental utilizado foi o de blocos ao acaso, em esquema fatorial [(5+1)x2], com três repetições. Os tratamentos foram constituídos de cinco diferentes fertilizantes NPK+Zn (quatro fontes com Zn e uma sem Zn), um tratamento sem adubação e duas doses de adubação (uma vez e o seu dobro). Com base nos resultados obtidos foi concluído que a aplicação dos tratamentos disponibilizou Cd, Pb e Cr para as plantas de soja e para o solo do experimento nas duas doses de adubação utilizadas.<br>Fertilizers used to supply micronutrients may have toxic heavy metals in their composition, which can have severe consequences for the environment. Plants grown in the presence of certain concentrations of toxic elements may present a risk of contamination because the toxins accumulate in their tissues. This study aimed to measure the presence of the toxic heavy metals Cd, Pb and Cr in the soil and leaf tissue of field-grown soybean plants, fertilized with a formulated N:P2O5:K2O and different sources of Zn. The experimental design utilized randomized blocks in a factorial scheme [(5+1)x2], with three replications. The treatments consisted of five different fertilizers NPK + Zn (four sources with Zn and one without Zn), a treatment without fertilizer and two fertilizer levels (a single and double application). Based on obtained results it was concluded that the double application of the treatments released Cd, Pb and Cr into the soybean plants and experiment