Exfoliated buccal and microdissected lung cell expression of antioxidant enzymes

Introduction: An exfoliated buccal cell biomarker assay for antioxidant gene transcript levels was used to measure inter-tissue concordance with lung, and inter-subject variability in a lung cancer case-control study. Methods: First, qualitative RNA-specific RT-PCR was used to compare expression in exfoliated buccal cells with that in laser microdissected lung tissue remote from the tumor from 14 individuals providing both specimens. Results: There was complete [100% for quinone oxidoreductase 1 (NQO1), glutathione peroxidase (GPX), and superoxide dismutase 1 (SOD1)], or predominant [85.7% for catalase (CAT)] inter-tissue concordance for qualitative expression. Second, quantitative real-time RT-PCR for antioxidant enzyme transcript levels was performed in exfoliated buccal samples from these same 14 individuals, as well as 28 additional individuals providing buccal cells only, for a total of 42 buccal specimens (19 current smokers and 23 ex- or never-smokers), of whom 26 (61.39%) had a new diagnosis of lung cancer. Discussion: Wide inter-individual expression differences for each gene transcript (>10¹-10⁴-fold) were observed in the exfoliated buccal cells, unrelated to smoking and case-control status. In multivariate analyses, family history of tobacco-related malignancy correlated inversely with buccal NQO1 and CAT mRNA levels (p = 0.003, p < 0.001, respectively). This antioxidant expression trait may relate to family risk of cancer, but is notably unrelated to oxidant challenges inherent in cigarette smoke.