S0424 - Carcinogens in Lung Tissue From Smokers (Closed to Entry as of 7/15/07) and Non-Smokers With Newly Diagnosed Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Observational

Summary: 
      RATIONALE: Studying samples of blood and tissue from smokers (closed to entry as of 7/15/07)
      and non-smokers with cancer in the laboratory may help doctors learn more about changes that
      occur in DNA and identify biomarkers related to cancer. It may also help doctors learn more
      about risk factors for lung cancer and may help the study of cancer in the future.

      PURPOSE: This clinical trial is studying carcinogens in lung tissue from smokers (closed to
      entry as of 7/15/07) and non-smokers with newly diagnosed stage I, stage II, or stage III
      non-small cell lung cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Assess lung tissue from patients with stage I, stage II, stage IIIA, or stage IIIB
           non-small cell lung cancer for specific tobacco smoke carcinogens (including polycyclic
           aromatic hydrocarbons [PAH] and DNA adducts, alterations in specific genes, including
           p53 and K-ras, and expression of HER2 and estrogen receptors α and β).

        -  Determine whether tobacco smoke carcinogens differ by gender and smoking status,
           adjusting for potential exposures and influential factors, including family smoking
           status, medication use, and hormonal and reproductive factors.

        -  Measure the levels of PAH-DNA adducts in lymphocytes and lung tissue and examine
           correlations between the two tissue sources.

        -  Determine whether DNA damage levels in tissue as well as in lymphocytes are higher in
           females than in males for the same level of smoking.

        -  Determine polymorphisms in several genes involved in the metabolism of the specific
           carcinogens investigated and in steroidogenesis and metabolism.

        -  Summarize patient self-report questionnaire data on active and passive smoking, other
           carcinogenic exposures, smoking preference, economic and educational status, family
           smoking status, reproductive factors, weight loss, and medication use by categories of
           male versus female and never-smoker versus ever-smoker.

      OUTLINE: This is a case-series, multicenter study. Patients are stratified according to
      gender and smoking status (never smoker [< 100 cigarettes smoked during lifetime] vs ever
      smoker [≥ 100 cigarettes smoked during lifetime] [closed to accrual as of 7/15/07]).

      Patients complete the Lung Cancer Epidemiology Questionnaire for detailed assessment of the
      following:

        -  Exposure to active and passive smoke

        -  Occupational exposures

        -  Reproductive and hormonal risk factors

        -  Weight loss

        -  Economic and educational status

        -  Family smoking status

        -  Medication use

        -  Other variables relevant for the analysis (e.g., HER2, estrogen receptor status)
           Peripheral blood samples are collected for research studies. Previously collected tissue
           samples are also studied in the laboratory. Samples are examined for DNA adduct levels.
           Estrogen receptor α and β are assessed by immunohistochemistry (IHC). HER2 expression
           and amplification are measured by chromogenic in situ hybridization. IHC and
           DNA-polymerase chain reaction (PCR)-single-stranded conformational polymorphism assay
           are used to analyze p53 mutations. RAS mutations are analyzed with restriction fragment
           length polymorphism-PCR assay. Polycyclic aromatic hydrocarbons and 4-aminobiphenyl-DNA
           damage are assessed by IHC and immunofluorescence. Matrix-assisted laser
           desorption/ionization time of flight mass spectrometry is used to genotype
           polymorphisms, including CYP1A1, CYP1B1, GSTM1, GSTP1, MPO, NAT-1, NAT-2, CYP19, CYP17,
           SULT1A1.

      Patients are followed annually for up to 5 years.

      PROJECTED ACCRUAL: A total of 900 patients will be accrued for this study (female and male
      smoker strata closed to accrual as of 7/15/07).
    

Intervention name(s): chromogenic in situ hybridization; gene expression analysis; mutation analysis; polymerase chain reaction; polymorphism analysis; fluorescent antibody technique; immunohistochemistry staining method; laboratory biomarker analysis; matrix-assisted laser desorption/ionization time of flight mass spectrometry; study of socioeconomic and demographic variables; study of high risk factors
Intervention type(s): Genetic; Genetic; Genetic; Genetic; Genetic; Other; Other; Other; Other; Other; Procedure
Intervention MeSH terms: Antibodies
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Cancer center
      
Keywords: stage IIIB non-small cell lung cancer; stage IIIA non-small cell lung cancer; stage IA non-small cell lung cancer; stage IB non-small cell lung cancer; stage IIA non-small cell lung cancer; stage IIB non-small cell lung cancer