Trial Information

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.

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).