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

Background: 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. Methods: 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. Results: 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). Conclusions: The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.

Parasitological risk assessment from wastewater reuse for disposal in soil in developing countries

The purpose of this work is to analyze the parasitological risks of treated wastewater reuse from a stabilization pond in the city of Piracicaba, in the State of Sao Paulo (Brazil), and the level of treatment required to protect public health. Samples were taken from raw and treated wastewater in stabilization ponds and submitted to a parasitological, microbiological and physicochemical analysis. The study revealed on treated wastewater the presence of Ascaris sp. and Entamoeba coli with an average density of 1 cysts L-1 and 6 eggs L-1, respectively. For Ascaris, the annual risks of infection due to the accidental ingestion of wastewater irrigation were 7.5 x 10(-2) in 208 days and 8.7 x 10(-2) in 240 days. For Total Coliforms and Escherichia coli in treated wastewater, the average density was 1.0 x 10(5) MPN/100 ml and 2.7 x 10(4) MPN/100 ml respectively, representing 99% and 94% removal efficiency, respectively. For BOD, COD, TS and TSS removal efficiency was 69, 80, 50 and 71%, respectively. The removal efficiency for nitrogen; ammonia nitrogen and total phosphate was 24, 19 and 68%, respectively. The average density of helminths eggs in treated wastewater is higher compared to the density of the limit value of <= 1 egg L-1 and tolerable risk is above the level recommended by the World Health Organization. Multiple barriers are necessary for the reduction of organic matter, chemical contaminants and parasites from treated wastewater. Standards for the sanitary control of treated wastewater to be reused in agricultural irrigation areas should be compiled for developing countries in order to minimize public health risks.