Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis.

Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis.
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DOI:
10.1158/0008-5472.can-09-1568
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发表时间:
2009-11-15
期刊:
影响因子:
11.2
通讯作者:
Willey JC
Willey JC
中科院分区:
医学1区
文献类型:
--
作者:
Blomquist T;Crawford EL;Mullins D;Yoon Y;Hernandez DA;Khuder S;Ruppel PL;Peters E;Oldfield DJ;Austermiller B;Anders JC;Willey JC

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In previous studies we reported that key antioxidant and DNA repair genes are regulated differently in normal bronchial epithelial cells (NBEC) of lung cancer cases compared to non-lung cancer controls. In an effort to develop a biomarker for lung cancer risk, we evaluated transcript expression of 14 antioxidant, DNA repair and transcription factor genes in NBEC (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 (ROC) area under the curve (AUC) was 0.82 (95% CI, 0.68 – 0.91) for the first case-control set (25 lung cancer cases and 24 controls), and 0.87 (95% CI, 0.73 – 0.96) for the second set (18 cases and 22 controls). For each gene comprised by the test, the key difference between cases and controls was altered distribution of transcript expression among cancer cases compared to controls, with more lung cancer cases expressing at both extremes among all genes (K-S test, D=0.0795; P=0.041). A novel statistical approach was used to identify for each gene the lower and upper boundaries of transcript expression that optimally classifies cases and controls. Based on the data presented here, there is 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 level in normal airway epithelium.