Prospective Analysis of Genotypes in Adults Undergoing Therapy for Lung Cancer
- 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
- Many of these differences have not been extensively explored in patients with lung
- 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.
- All individuals with the diagnosis of lung cancer being treated at the Washington D.C.
Veteran's Affairs Hospital, Washington Hospital Center (WHC) or the Medical Oncology Branch
of the National Cancer Institute (NCI).
- 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, and OCT2 will be analyzed by the Clinical Pharmacology
- 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
Hospital, WHC, 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 (grades 3-5), 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.
Time Perspective: Prospective
Arun Rajan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|VA Medical Center, Washington D.C.||Washington, District of Columbia 20422|