An analysis of DNA repair as a determinant of survival in patients with non-small-cell lung cancer.

Abstract

Non-small-cell lung cancer (NSCLC) is frequently resistant to chemotherapy, and this resistance has been associated with elevated nucleotide excision repair (NER) in tumor tissue. We hypothesized that patients with NSCLC who had effective systemic (host) NER would have poorer survival than patients with suboptimal NER and that the association between NER effectiveness and survival would be most marked in patients receiving chemotherapy. 375 patients with newly diagnosed NSCLC were accrued for a case-control study between July 1995 and December 1999. NER activity was estimated as the DNA repair capacity (DRC) measured in the patient's peripheral lymphocytes by the host cell reactivation assay. Cox proportional hazards models were used to assess the association between DRC and survival. All statistical tests were two-sided. For every unit (percentage) increase in DRC, the relative risk (RR) of death was 1.05 (95% confidence interval [CI] = 1.00 to 1.10; P =.05) for the 345 patients for whom weight loss information was available and 1.06 (95% CI = 1.00 to 1.12; P =.03) for the 275 patients with complete follow-up information. In 86 patients treated with chemotherapy only, the RR of death increased to 1.11 (95% CI = 1.02 to 1.21; P =.01) for every unit (percentage) increase in DRC. Of those 86 patients, patients in the top quartile of the DRC distribution were at twice the RR of death as those in the lowest quartile (RR = 2.72; 95% CI = 1.24 to 5.95; P =.01). Effective DRC was not a risk factor for death in patients who were not treated with chemotherapy. Our data suggest that effective host DRC may be associated with poorer survival in patients with NSCLC who are treated with chemotherapy.