RESUMO
We investigated the possible influence of 86 single-nucleotide polymorphisms (SNPs), known to associate with the risk of colorectal cancer (CRC), on overall survival and time to recurrence (TTR) in 733 Italian CRC patients followed up for up to 84 months after surgery. In the Cox multivariate analysis, adjusted for gender, age, pathological stage and adjuvant chemotherapy (yes/no), the risk of death significantly increased by rare allele count (P<0.05) for rs1801133 (MTHFR), rs4939827 (SMAD7), rs2306283 (SLCO1B1) and rs12898159 (BMP4), whereas for rs736775 (GPX3) the opposite was observed. Two additional SNPs associated with TTR, namely rs16892766 (downstream of EIF3H) and rs10749971 (COLCA2). Our findings show that some genetic variants previously found to associate with CRC risk are also associated with survival after treatment. The identification of alleles defining subgroups of patients with worse clinical outcome may have application in developing pharmacogenetic strategies aimed at personalizing CRC treatment.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , Adenocarcinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias Colorretais/diagnóstico , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Risco , Adulto JovemRESUMO
Evidence in animal models has suggested an association between susceptibility to lung tumorigenesis and gene-expression profiles in normal lung. Here, we compared RNA pools from normal lung tissue of lung adenocarcinoma patients (cases) or non-lung cancer patients (controls) by hybridization of whole-human genome expression arrays. Principal component analysis identified a gene-expression signature of 85 genes that distinguishes cases from controls as well as smokers from nonsmokers. Elevated mRNA levels of one of these genes, AZGP1, were significantly associated with disease status. These results support the hypothesis that differences in the gene-expression levels of the normal tissue may be predictive of genetic predisposition to lung cancer in humans.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/genética , Glicoproteínas/genética , Pulmão/metabolismo , RNA Mensageiro/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adipocinas , Idoso , Biomarcadores Tumorais/genética , Western Blotting , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de TecidosRESUMO
Nonspecific X-linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X-linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2-26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081.
