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.

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).

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer

  • Stage I, II, IIIA, or IIIB (T4 or N3) disease

  • No malignant pleural effusion; if pleural fluid is present, 1 of the following criteria must be met:

    • Benign pleural fluid
    • Pleural fluid is due to prior thoracotomy
    • Pleural fluid is deemed too small to safely tap

  • No diagnosis by cytology alone

• Newly diagnosed disease

• Must have tumor blocks/slides available and must be willing to provide tissue samples

• Prior smoking history meeting 1 of the following criteria:

  • Never smoker, defined as < 100 cigarettes in lifetime
  • Former smoker, defined as no smoking for ≥ 1 year
  • Current smoker, defined as all others (closed to accrual as of 7/15/07)

• No pericardial effusions

PATIENT CHARACTERISTICS:

• No other prior malignancy except for 1 of the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • In situ cervical cancer
  • Other cancer for which the patient has been disease free for five years

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy
• Concurrent participation in therapeutic trials allowed

Cancer center