Abstract 1488: Inter-individual variation in hTERT regulation pathway genes in normal bronchial epithelial cells

Abstract

Abstract Background: Genome-wide association studies (GWAS) and candidate gene studies suggest that telomere maintenance genes participate in etiology of lung cancer, idiopathic pulmonary fibrosis, and COPD. Telomeres are nucleoprotein structures located at the end of chromosomes that are maintained by telomerase encoded by hTERT. Telomerase is active in cancers, has the ability to aid in rapid cell division, and is dysfunctional in chronic conditions induced by inflammation as such as diabetes, renal failure, and COPD. hTERT is a known downstream target of β-catenin and WNT signaling. However, little is known regarding expression levels of these genes in normal bronchial epithelial cells (NBEC). The purpose of this study is to investigate inter-individual variation in regulation of β-catenin and WNT in NBEC, and if present, identify variants in regulatory region of human telomerase reverse transcriptase (hTERT) that could be used as candidate biomarkers for lung cancer risk. Methods: NBEC specimens from subjects with COPD (n=5) or without COPD (n=9) were obtained by bronchoscopy brush under IRB approved protocol. β-catenin, and WNT4 were measured by competitive multiplex-RT-PCR. Results: Both β-catenin and WNT4 displayed significant inter-individual variation as measured by Intra-Class Correlation (ICC) analysis (β-catenin ICC = 0.47, 95% Confidence Interval (0.2, 0.55), p < 0.05; WNT4 ICC = 0.60, 95% Confidence Interval (0.35, 0.85), p < 0.05). In patients with COPD, WNT4 expression was significantly higher in current smokers compared to former smokers (p<0.05). Conclusions: Inter-individual variation in NBEC expression of β-catenin and/or WNT4 was observed and it is reasonable to test the hypothesis that these genes and related pathway genes may contribute to variation in regulation of hTERT in NBEC and risk for lung cancer, COPD, and/or other lung diseases. Citation Format: Rose Zolondek, Daniel J. Craig, Erin L. Crawford, James C. Willey. Inter-individual variation in hTERT regulation pathway genes in normal bronchial epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1488.