RESUMO
MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value = 1.7 × 10(-4) ; odds ratio, OR = 1.72; 95% confidence interval, CI = 1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value = 5.38 × 10(-3) ; OR = 0.56, 95% CI = 0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value = 5.40 × 10(-3) ; OR = 1.41, 95% CI = 1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.
Assuntos
Adenocarcinoma/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Cromossomos Humanos Par 7/genética , Cromossomos Humanos X/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , População BrancaRESUMO
OBJECTIVE: Heroin use has stabilized in recent years in Spain, and the use of injected heroin having decreased. Nevertheless,major differences exist among different Autonomous Communities and among injected heroin users profile. This study is aimed at ascertaining the forms of heroin use (how administered) in an intentional sample of users in a situation of social exclusion andsome variables related to said forms of use. METHODS: The sample was comprised of 285 participants (82.8% males; average age 36.06). This study was conducted in the city of Granada in July-October 2002. Structured surveys conducted by onthe-street interviewers and individuals having knowledge of the environment («peers¼) using the «snowball¼ technique. RESULTS: A total of 48.4% of the participants alternate inhaled and intravenous heroin use; 25.6% using only inhaled and 25.6% only intravenous. Following a regression analysis, it was found that the females, the youngest users and those having started use at an older age were at less risk of intravenous heroin use. A total of 21.5% of the participants who started using heron in inhaled form, also currently use both the injected and inhaled forms, the remaining 79.5% continue to use the inhaled form. CONCLUSIONS: Among individuals in a situation of social exclusion the intravenous form exceeds the estimated percentages in the Autonomous Community of Andalusia.
OBJETIVO: En los últimos años el consumo de heroína en España se ha estabilizado y el uso de la vía inyectada ha disminuido. No obstante existen importantes diferencias entre comunidades y entre los consumidores por la vía inyectada. El objetivo del presente estudio es conocer vías de administración de heroína en una muestra intencional de usuarios en situación de exclusión social y algunas de las variables que se asocian con ellas. METODOS: La muestra se compone de 285 participantes (hombres 82,8%; edad media 36,06). El estudio se llevó a cabo en la ciudad de Granada entre julio y octubre de 2002. Se realizaron entrevistas estructuradas por trabajadores de calle y personas conocedoras del medio (iguales), utilizando la técnica de «bola de nieve¼. RESULTADOS: El 48,4% de los participantes consumen heroína por vía pulmonar e intravenosa; el 25,6% la consumen sólo por vía pulmonar; y un 25,6% sólo intravenosa. Tras un análisis de regresión se observa que las mujeres, los participantes más jóvenes y los que se han iniciado más tarde en el consumo son quienes menos tienden a utilizar la vía intravenosa. De los participantes que se iniciaron con inhalación el 21,5% actualmente además de inhalar también se inyectan, y el 79,5% restante se mantiene en la vía por inhalación. CONCLUSIONES: Las personas en situación de exclusión social utilizan la vía intravenosa en porcentajes superiores al resto de la comunidad andaluza.