Prospective Analysis of Genotypes in Adults Undergoing Therapy for Lung Cancer
Condition: Carcinoma, Non-Small Cell Lung; Carcinoma, Small-Cell Lung
MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Small Cell Lung Carcinoma
Study type: Observational

Summary: 
      Background:

        -  The Lung Cancer section of the National Cancer Institute s Medical Oncology Branch is
           running a study to better understand which genes might be important in patients who are
           undergoing therapy for lung cancer.

      Objectives:

        -  To find out if differences (also called polymorphisms) in specific genes lead to
           differences in outcomes (such as treatment success and survival rates) for patients who
           have been diagnosed with lung cancer.

        -  To establish a repository of genetic information for future studies of these differences
           and their relation to lung cancer.

      Eligibility:

        -  Any individual who has been diagnosed with lung cancer and is being treated through the
           National Cancer Institute.

      Design:

        -  After entrance in this study, patients will provide information to the researchers on
           age, gender, race/ethnicity, treatments received and response to treatments, and other
           specific information about their disease. This information will be kept confidential.

        -  Approximately half a tablespoon of blood will be drawn.

        -  Patients will be treated for lung cancer with normal treatment methods, as if they had
           not been enrolled in the study

        -  Some patients may be offered the option of enrolling in separate research protocols for
           cancer treatment, involving chemotherapy, surgery, or radiation.
    

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.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: NSCLC; Genotype; SCLC; Lung Cancer; Non-Small Cell Lung Cancer; Small Cell Lung Cancer