Prospective Analysis of Genotypes in Adults Undergoing Therapy for Lung Cancer

Brief Summary

Detailed Description

Background: * Lung cancer is the leading cause of cancer deaths among men and women worldwide. * Despite modern surgical, radiation, and chemotherapeutic interventions, the prognosis for patients with lung cancer remains poor, with an overall cure rate of less than 15%. * Genetic polymorphisms in drug-metabolizing enzymes, transporters, growth factor and hormonal receptors, DNA repair enzymes, and transcription factors might affect an individual s response to chemotherapy and radiation. * Interindividual differences in efficacy and toxicity of cancer chemotherapy and radiation are especially important given the narrow therapeutic index of these modalities. * Many of these differences have not been extensively explored in patients with lung cancer. Objectives: * To better understand the genotype-phenotype relationship between genetic polymorphisms and clinical outcomes, with a focus on overall survival, following lung cancer therapy. * To better understand differences in outcome between Caucasian and African American patients being treated for lung cancer as a function of genotype. * To establish a DNA repository for the investigation of polymorphisms related to outcomes in lung cancer. * To develop methodology for the isolation, enumeration and live cell culture of circulating tumor cells (CTC) from lung cancer patients with microfiltration devices. Eligibility: - All individuals with the diagnosis of lung cancer being treated at the Washington D.C. Veterans Affairs Medical Center or the Medical Oncology Branch of the National Cancer Institute (NCI). Design: * A single 7-ml sample of venous blood will be obtained from all patients enrolled onto this study, for isolation of DNA. * Two 5 ml samples of venous blood, drawn immediately following the 7 ml sample, will be obtained from all patients enrolled on this study at the NCI Clinical Center (only), for CTC studies. * Polymorphisms in the following genes: ABCB1, ABCG2, COMT, CYP17, CYP19, CYP1B1, CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2J2, CYP3A4, CYP3A5, DPYD, EPHX2, ERalpha, ERbeta, ERCC1, ERCC2, GSTP1, HIF1A, MPO, MTHFR, NQO1, p53, PPARD, SLCO1B3, TYMS, UGT1A1, VEGF, VEGFR, EGFR, SLC28A1, CDA, XRCC1, OCT1, OCT2, CHRNA3 and CHRNA5 will be analyzed by the Clinical Pharmacology Program. * Methodology for the isolation, enumeration, and live cell culture of CTC with microfiltration devices will be developed by the NCI Genetics Branch. * Patients will be followed at the medical oncology clinic at the Washington DC VA Medical Center or the NCI and the following information will be recorded in a confidential database: age, gender, race/ethnicity, smoking history, histology, stage, treatment(s) received, response, toxicity, time to disease progression, time to death. * Associations between genetic polymorphisms and response to therapy, toxicity and clinical outcomes will be analyzed. * The results of the CTC studies will be applied to the initial development and clinical validation of CTC technology and lung cancer assays.

Primary Outcomes