RESUMO
OBJECTIVE: Gemcitabine-based chemotherapy is regarded as the standard treatment for biliary tract cancer (BTC). Potential biomarkers for gemcitabine response include the activities of cytidine deaminase (CDA), human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (DCK), and ribonucleotide reductase M1 (RRM1). Here, we investigated whether single nucleotide polymorphisms (SNPs) in their encoding genes were associated with the efficacy of gemcitabine chemotherapy in treating BTC. METHODS: We retrospectively evaluated 11 SNPs in the CDA, hENT1, DCK, human concentrative nucleoside transporter 3 (hCNT3), and RRM1 genes in 80 patients with unresectable, metastatic, or recurrent BTC who were treated with gemcitabine plus cisplatin. RESULTS: After the results were adjusted for clinical predictors, the variant allele of rs1048977 in the CDA gene was associated with tumor response in a dominant model (OR, 0.23; 95% CI, 0.06-0.93; p = 0.039). No significant association was detected between the 11 SNPs and grade 3/4 toxicity. CONCLUSIONS: Our findings suggest that the polymorphism of CDA may be a potential predictive marker for the efficacy of gemcitabine-based chemotherapy in patients with BTC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/genética , Biomarcadores Tumorais/genética , Citidina Desaminase/genética , Recidiva Local de Neoplasia/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina Quinase/genética , Transportador Equilibrativo 1 de Nucleosídeo/genética , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Ribonucleosídeo Difosfato Redutase , Taxa de Sobrevida , Proteínas Supressoras de Tumor/genética , GencitabinaRESUMO
PURPOSE: Postoperative recurrence in stage I non-small cell lung cancer (NSCLC) is the major cause of a poor prognosis. This study aims to identify genetic variants that are associated with the prognosis of early-stage NSCLCs. EXPERIMENTAL DESIGN: A genome-wide association study (GWAS) was conducted in 250 patients in stage I NSCLCs and the results were replicated in additional 308 patients. RESULTS: Results from an Affymetrix Genome-wide Human SNP array in 250 patients identified 94 SNPs with significant associations (P < 2 × 10(-4)), which were selected for replication in 308 additional patients. Pooled analysis of the 558 patients determined that rs1454694 in chromosome 4q34 was the most significant marker of lung cancer prognosis in the stage I patients (adjusted HR = 2.81; P = 5.91 × 10(-8)). After the candidate loci were mapped, an additional four markers at chromosome 4q34.3 were significantly associated with recurrence-free survival (RFS; P < 5 × 10(-5)). A haplotype of five SNPs in 4q34 also showed significant association with RFS (P = 4.29 × 10(-6)). CONCLUSIONS: A genetic polymorphism rs1454694 was identified as a novel genetic risk factor for RFS of stage I NSCLCs. This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLCs.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Polimorfismo de Nucleotídeo Único/genética , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Mapeamento Cromossômico , Cromossomos Humanos Par 4/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Período Pós-Operatório , PrognósticoRESUMO
BACKGROUND/AIMS: The human leukocyte antigen (HLA) system is an integral component of immune response. Highly polymorphic HLA genes may play a pivotal role in the response of antiviral therapy. We investigated the effects of HLA gene polymorphism on the clinical outcome of chronic hepatitis B patients who received lamivudine treatment. METHODS: Depending on their clinical response to lamivudine therapy, a total of sixty one patients were divided into following groups; non-responders, viral breakthroughers, relapsers, and seroconverters. HLA-A, -B, -Cw, -DRB and HLA-DRB1 alleles typing was performed on each group through the polymerase chain reaction and the sequence-specific oligonucleotide hybridization method. The distribution patterns of HLA-A, HLA-B, HLA-Cw, HLA-DRB, and HLA-DRB1 were then analysed. RESULTS: When non-responders were compared to the other groups, high frequencies in HLA-Cw1, HLA-DRB14 and HLA-DRB4 (p=0.015, 0.033 and 0.004 respectively) were evident. When seroconverters were compared to viral breakthroughers, high frequencies in HLA-A2 and HLA-DRB4 (p=0.048, 0.025 respectively) were evident. CONCLUSIONS: Our data suggests that HLA-A2, HLA-Cw1, HLA-DRB14 genes are related to the clinical outcomes of lamivudine treatment in chronic hepatitis B patients. These genes may be used in the prediction of the clinical outcome of lamivudine therapy in chronic hepatitis B patients.
