Literature DB >> 19018088

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

Hong-Tae Kim1, Jong-Eun Lee, Eun-Soon Shin, Yeon-Kyeong Yoo, Jae-Hwa Cho, Min-Hye Yun, Yeul-Hong Kim, Se-Kyu Kim, Hyun-Jung Kim, Tae-Won Jang, Seung-Min Kwak, Chul-Soo Kim, Jeong-Seon Ryu.   

Abstract

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.

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Year:  2008        PMID: 19018088     DOI: 10.1200/JCO.2008.16.6496

Source DB:  PubMed          Journal:  J Clin Oncol        ISSN: 0732-183X            Impact factor:   44.544


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