RESUMEN

BACKGROUND: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. MATERIALS AND METHODS: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. RESULTS: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. CONCLUSIONS: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.

Asunto(s)

Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Codón/genética , Proteínas de Unión al ADN/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético/genética , Adenocarcinoma/patología , Arginina/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , ADN/análisis , ADN/genética , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Glutamina/genética , Humanos , India , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X

RESUMEN

BACKGROUND: The wide spectrum of clinical features in advanced stages of non-small cell lung cancer (NSCLC) probably contributes to disparities in outcomes because of different prognostic variables significant for stage IIIB/IV patients. Hence the aim of this study was to check for favorable response of patients to various chemotherapeutic combinations with respect to patient survival in stage IIIB and stage IV NSCLC disease. We selected those patients for our study who were receiving treatment with paclitaxel, gemcitabine or etoposide in combination with platinum based drugs. MATERIALS AND METHODS: Seventy-two patients who visited the hospital from June 2009 to November 2012 with confirmed diagnosis of lung cancer were included, and data were collected for follow up and classified according to treatment received with respect to patients' regimen and response, and overall survival. This study analyzed tumor variables that were associated with clinical outcome in advanced NSCLC patients who were undergoing first-line chemotherapy for stage IIIB/IV NSCLC. RESULTS: Comparative data on various parameters like age, gender, stage, histology, site of disease, metastatic site and chemo-regimens was analyzed; these parameters predicted variable significant improvement for overall survival (p≥0.05). One and two year survival rates were 20.8% and 15.3% . CONCLUSIONS: In this study we found slight improvement in survival rates in NSCLC and clinical outcomes with one combination (carboplatin+paclitaxel). Overall there were only marginal differences in survival rates for other chemo-regimens evaluated in this study.

Asunto(s)

Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/mortalidad , Neoplasias Pulmonares/mortalidad , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Gemcitabina

RESUMEN

BACKGROUND: The Stroop paradigm evaluates susceptibility to interference and is sensitive to dysfunction in frontal lobes and drug effects. The aim of the present study was to establish a simple and reliable computerized version of Stroop color-word test, which can be used for screening of various psychotropic drugs. MATERIALS AND METHODS: The standardized method was followed in all cases, by recording the reaction time (RT) in msec in 24 healthy participants using computerized version of Stroop color-word test. Reproducibility of the test procedure was evaluated by recording the RTs by a single experimenter on two sessions (interday reproducibility). Validity of the model was further tested by evaluating the psychotropic effect of Zolpidem 5 mg, Caffeine 500 mg, or Placebo on 24 healthy subjects in a randomized, double blind three-way crossover design. RESULTS: The method was found to produce low variability with coefficient of variation less than 10%. Interday reproducibility was very good as shown by Bland-Altman plot with most of the values within ±2SD. There was a significant increase in RTs in Stroop performance with Zolpidem at 1 hr and 2 hrs; in contrast, caffeine significantly decreased RTs in Stroop performance at 1 hr only compared to placebo. CONCLUSION: The Stroop color-word recording and analysis system is simple, sensitive to centrally acting drug effects, and has potential for future experimental psychomotor assessment studies.