Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Análisis de estarategias de atención primaria de salud en el municipio de Malvinas Argentinas: Un abordaje cuanti-cualitativo

La situación de salud en Argentina revela la necesidad de evaluar la capacidad de gestión de centros de primer nivel de atención y el desarrollo de redes asistenciales. El objetivo de este proyecto fue evaluar las estrategias de atención primaria en los centros de salud de la comunidad de Malvinas Argentinas. La metodología consistió en una fase diagnóstica, una de intervención y validación de la propuesta y una de análisis de resultados, abordada con metodología cuantitativa y cualitativa. Este trabajo movilizó el abordaje de la salud desde la atención primaria y el reconocimiento de los propios centros de generar estrategias para brindar atención efectiva y eficiente a pesar del deterioro socioeconómico de la comunidad. Además permitió identificar el funcionamiento de una red comunitaria, en la cual será necesario afianzar el trabajo respecto a la educación en salud. El impacto de la presente investigación está relacionado a las vinculaciones que se generaron entre las instituciones involucradas

Analysis of user satisfaction in primary health care centers in the province of Cordoba, Argentina

Objetivo: Identificar el nivel de satisfacción de los destinatarios de los centros de salud de la provincia de Córdoba. Método: Se implementó encuestas a los destinatarios de los centros de salud de la provincia de Córdoba indagando acerca de aspectos sociodemográficos, tipo de asistencia sanitaria, motivo de consulta, accesibilidad y opinión general de la atención recibida. La información recabada fue procesada y analizada de acuerdo a la naturaleza de la variable y las comparaciones se efectuaron por ANOVA y para datos categorizados se utilizó coeficiente de contingencia (nivel de significación 0,05). Resultados: El acceso geográfico fue considerado aceptable por los encuestados al igual que el tiempo de espera y las condiciones edilicias. El desempeño profesional durante la atención, el vínculo establecido entre el profesional y el destinatario y el servicio brindado por el centro de salud fueron factores valorizados por los encuestados. Conclusión: El análisis de la satisfacción de los destinatarios de los centros de salud es importante para proporcionar información válida para generar respuestas oportunas y optimizar los recursos sanitarios.ABSTRACT Objective: To identify users´ satisfaction about services provide for health centers in the province of Cordoba. Method: Surveys was implemented to the health centers´ users in the the province of Cordoba, asking about sociodemographic aspects, type of health care, motive of consultation, accessibility and general opinion about care received. The information collected was processed and analyzed according to the nature of the variable and comparisons were made by ANOVA and for data categorized coefficient of contingency was utilized (significance level 0.05). Results: Geographic access was considered acceptable by respondents as the waiting time and the conditions buildings. The professional performance during care, the link between the practitioner and users and the service provided by the health center were factors valued by respondents. Conclusion: The analysis of users´satisfaction of health centers is important to provide valid information for generate opportune answers and to optimize the sanitary resources

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC