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Lung cancer is the leading cause of cancer-related deaths in the US for both males and females. Furthermore, adenocarcinoma is now the most common lung malignancy in the US. Recent studies suggest that estrogen may contribute to the development of lung adenocarcinoma in women. The hypothesis of this study is that alterations in estrogen synthesis and estrogen/carcinogen metabolism within lung tissue contribute to the susceptibility of women for lung cancer development. Lung tissue was obtained from 11 female patients (7 ex-smokers and 4 never-smokers) diagnosed with Stage I lung adenocarcinoma. Laser capture microdissection was performed using the Pixcell II system (Molecular Devices) to isolate bronchoalveolar cells from 17 lung specimens (7 nonneoplastic and 10 neoplastic; matched tissues were obtained from 6 individuals). RNA was extracted using the RiboAmp Kit (Molecular Devices), and its quality and quantity were estimated using a Bioanalyzer (Agilent Technologies). Quantitative real-time PCR was used to determine the level of expression of 15 genes involved in either local estrogen synthesis (CYP11B1, CYP17A1, CYP19 (aromatase), CYP21, HSD3B1, HSD17B1, HSD17B3, HSD17B7) or estrogen/carcinogen metabolism (CYP1A1, CYP1B1, GSTα4, GSTM1, GSTT1, NQO, COMT). For each gene, the expression level was normalized using the HPRT gene. The Wilcoxon signed rank test was used to test for differences between normalized data from the 6 matched samples. The percentage of samples with detectable expression levels did not differ significantly with respect to tissue type (nonneoplastic vs. neoplastic) and smoking status (never-smokers vs. ex-smokers) for most genes studied. Expression of CYP19 was not detectable in nonneoplastic samples but was present in 60% of the neoplastic samples. Expression of CYP21, HSD17B3, HSD17B7 was detected in 70-100% of the samples, while only approximately 50% of the samples expressed CYP17A1 and HDS17B1. Less than 20% of the specimens expressed HSD3B1, and CYP11B1 was not detected in any sample. The estrogen/carcinogen metabolism genes CYP1B1, GSTα4, GSTT1, NQO and COMT were expressed in all samples. In contrast, CYP1A1 and GSTM1 were detected in less than 30% of the samples. Finally, statistical analyses indicate that no gene was differentially expressed in nonneoplastic and neoplastic samples. Additional analyses are in progress and include increasing the amount of input cDNA in cases where gene expression was not detected and evaluating samples obtained from current smokers. This study represents the first investigation of the expression of estrogen synthesis and metabolism genes within a pure population of bronchoalveolar cells. (Supported by fellowships from the AACR-Pennsylvania Department of Health and the ASPO/CRPF).

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA