Molecular Epidemiology Case-Series Study of Non-Small Cell Lung Cancer in Smoking and Non-Smoking Women and Men

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.