title: ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy.
abstract: Excision repair cross-complementation group 1 (ERCC1) is a highly conserved protein and an essential member of the nucleotide excision repair pathway. DNA repair is an important mechanism for resistance to platinum-based chemotherapy. Previous studies have shown that ERCC1 gene expression is associated with clinical outcome to platinum chemotherapy in a variety of cancers. Recently, 2 common polymorphisms in the ERCC1 gene have been described. The first is a single nucleotide polymorphism at codon 188 of the ERCC1 gene that causes a C-->T change but codes for the same amino acid, asparagine. This polymorphism may be associated with differential ERCC1 gene expression. The second is also a signal nucleotide polymorphism in the 3'-untranslated region and may affect MRNA stability. We hypothesized that these 2 polymorphisms may be associated with clinical outcome to platinum-based chemotherapy. We assessed the relationship between these ERCC1 gene polymorphism and clinical outcome to platinum-based chemotherapy in 106 patients with advanced refractory colorectal cancer. We found a significant associated between the ERCC1 codon 118 polymorphism and clinical outcome. Patients with the C/C genotype had a median survival of 15.3 months (95% CI, 6.0-12.1) and 11.1 months (95% CI, 5.8-16.2) for those with C/T and T/T genotypes, respectively. The ERCC1 codon 118 polymorphism may be a useful predictor of clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy.
authors.affiliation: University of Southern California/Norris Comprehensive Cancer Center, Los Angeles 90033, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Park
authors.forename: Wu
authors.initials: W
authors.lastname: Zhang
authors.forename: Jan
authors.initials: J
authors.lastname: Stoehlmacher
authors.forename: Denice
authors.initials: D
authors.lastname: Tsao-Wei
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Ji
authors.initials: J
authors.lastname: Gil
authors.forename: Jim
authors.initials: J
authors.lastname: Yun
authors.forename: Erin
authors.initials: E
authors.lastname: Sones
authors.forename: Nalin
authors.initials: N
authors.lastname: Mallik
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D005472:Fluorouracil