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 x 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.