Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis.
In previous studies, we reported that key antioxidant and DNA repair genes are regulated differently in normal bronchial epithelial cells of lung cancer cases compared with non-lung cancer controls. In an effort to develop a biomarker for lung cancer risk, we evaluated the transcript expressions of 14 antioxidant, DNA repair, and transcription factor genes in normal bronchial epithelial cells (HUGO names CAT, CEBPG, E2F1, ERCC4, ERCC5, GPX1, GPX3, GSTM3, GSTP1, GSTT1, GSTZ1, MGST1, SOD1, and XRCC1). A test comprising these 14 genes accurately identified the lung cancer cases in two case-control studies. The receiver operating characteristic-area under the curve was 0.82 (95% confidence intervals, 0.68-0.91) for the first case-control set (25 lung cancer cases and 24 controls), and 0.87 (95% confidence intervals, 0.73-0.96) for the second set (18 cases and 22 controls). For each gene included in the test, the key difference between cases and controls was altered distribution of transcript expression among cancer cases compared with controls, with more lung cancer cases expressing at both extremes among all genes (Kolmorogov-Smirnov test, D = 0.0795; P = 0.041). A novel statistical approach was used to identify the lower and upper boundaries of transcript expression that optimally classifies cases and controls for each gene. Based on the data presented here, there is an increased prevalence of lung cancer diagnosis among individuals that express a threshold number of key antioxidant, DNA repair, and transcription factor genes at either very high or very low levels in the normal airway epithelium.
Blomquist
Thomas
T
Department of Medicine and Pathology, University of Toledo Medical Center, Toledo, Ohio 43614, USA.
Crawford
Erin L
EL
Mullins
D'Anna
D
Yoon
Youngsook
Y
Hernandez
Dawn-Alita
DA
Khuder
Sadik
S
Ruppel
Patricia L
PL
Peters
Elizabeth
E
Oldfield
David J
DJ
Austermiller
Brad
B
Anders
John C
JC
Willey
James C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000502:physiology*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D020545:Respiratory Mucosa / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D014408:Biomarkers, Tumor