Abstract 2205: Identification of transcript abundance difference at lung cancer and COPD risk genes in normal bronchial epithelial cells

Abstract

Abstract Background: Lung cancer and chronic obstructive pulmonary disease (COPD) and are leading causes of morbidity and mortality both in the United States and worldwide. Inhalation of cigarette smoke is the primary known and preventable cause but only 10-15% of heavy smokers develop these diseases. This suggests that cigarette smoke exposure interacts with inherited susceptibility factors to determine risk. There is urgent need to identify heritable susceptibility factors that explain the majority of lung cancer and COPD risk. In prior studies, we and/or others have observed large inter-individual variation in normal bronchial epithelial cell (NBEC) expression of antioxidant, DNA repair, and cell regeneration control genes and altered regulation in NBEC of subjects with lung cancer or COPD. We collected normal bronchial epithelial cell (NBEC) samples from over 500 subjects with or demographically at risk for lung cancer. In this pilot study, we assessed total expression of multiple putative risk genes in NBEC samples from 78 subjects. Methods: A targeted competitive multiplex next generation sequencing (NGS) method (Blomquist et al, PLOS one 2013) was used to quantify transcript abundance at 70 marker sites among 33 target genes in NBEC total RNA from 78 subjects (18 cancer cases and 60 non-cancer controls). Approximately half of the cancer group (N = 10) and non-cancer group (N = 30) had COPD (FEV1/FVC<0.7). Results: TP73 was expressed higher and XRCC1 and MUC5B lower in cancer. GSTP1, MUC5B, OGG1, and TP73 were expressed at significantly higher level in COPD vs control by t-test in non-cancer group. Conclusions: This study of 78 subjects provides evidence for transcript abundance difference in selected genes with high prior likelihood for contributing to lung cancer and COPD risk. Those genes will be the focus of additional studies in BEC samples from over 500 subjects with or at risk for lung cancer and/or COPD in effort to further optimize current tests for lung cancer and COPD risk. Note: This abstract was not presented at the meeting. Citation Format: Jiyoun Yeo, Xiaolu Zhang, Erin Crawford, James Willey. Identification of transcript abundance difference at lung cancer and COPD risk genes in normal bronchial epithelial cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2205. doi:10.1158/1538-7445.AM2015-2205