title: Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy.
abstract: OBJECTIVE
  To determine whether germ-line variations in BRCA1 affect outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy.
  
  
  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).
  
  
  CONCLUSIONS
  These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Korea.
authors.forename: Hong-Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Eun-Soon
authors.initials: ES
authors.lastname: Shin
authors.forename: Yeon-Kyeong
authors.initials: YK
authors.lastname: Yoo
authors.forename: Jae-Hwa
authors.initials: JH
authors.lastname: Cho
authors.forename: Min-Hye
authors.initials: MH
authors.lastname: Yun
authors.forename: Yeul-Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: Se-Kyu
authors.initials: SK
authors.lastname: Kim
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Jang
authors.forename: Seung-Min
authors.initials: SM
authors.lastname: Kwak
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Jeong-Seon
authors.initials: JS
authors.lastname: Ryu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011379:Prognosis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D010984:Platinum; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases