Hprt mutant frequency and aromatic DNA adduct level in non-smoking and smoking lung cancer patients and population controls

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Abstract
T cell cloning and 32P-post-labelling methods were used to study the mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus and the aromatic DNA adduct level (AL) in peripheral lymphocytes of newly diagnosed lung cancer patients (92 ever-smokers and 87 never-smokers) and matched population controls (82 ever-smokers and 79 never-smokers). Overall, the MF (total mean 20.6×10–6) and AL (4.1×10–8) were similar in cases and controls with the same smoking status, indicating that the disease has limited effect on the two endpoints. When cases and controls were combined, the AL was significantly higher in current smokers than in former or never-smokers (P = 0.0003) and the MF was significantly higher in ever-smokers than in never-smokers (P = 0.004). Age affected the MF significantly in ever-smokers (1.6%/year, 95% CI 0.6–2.5, adjusted for packyears and years since last smoking), especially among cases (2.1%/year, 95% CI 0.5–3.7). An increase of AL with age was observed in currently smoking cases only (2.3%/year, 95% CI 0.3–4.2, adjusted for smoking dose). For currently smoking cases, there was also a more pronounced effect of smoking dose on both endpoints and a significant correlation between AL and MF (r = 0.52, P = 0.04) was observed among those with the highest dose. Our data also provide additional evidence for the different turnover times of smoking-induced DNA adducts and hprt mutations. The stronger increase of MF and AL with age and dose in currently smoking patients compared with controls is consistent with an interaction between smoking and genetic host factors.

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