Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy

Purpose: To determine whether germ-line variations in BRCA1 affect outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy. Patients and Methods: We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16%), IIIB (31%), and IV (53%). Results: The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3%) of the patients had squamous cell carcinomas and 137 (45.7%) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95% CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 × 10^-5), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677). Conclusion: These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.