Transcription factor-binding sites in the thymidylate synthase gene: predictors of outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin?
The identification of clinical and genetic parameters to predict the outcome in advanced colorectal cancer is a key issue in the management of this disease. We ascertained whether the clinical determinants of survival defined in a large cohort of patients treated with 5-fluorouracil (5-FU) (European Organization for the Research and Treatment of Cancer, EORTC model) also apply to 109 colorectal cancer patients receiving a therapy including oxaliplatin/5-FU as their first-line treatment. Our results confirm the considerable discriminatory power of the clinical model proposed in patients treated with a combined chemotherapy regimen. With the aim of identifying additional genetic prognostic parameters, we determined whether the polymorphisms in the promoter region of the thymidylate synthase (TS) gene that modifies the number of operative binding sites of a transcription factor (USF) could predict the clinical outcome of our patients and complement the EORTC clinical model. Our results indicate that this new genetic parameter (the number of USF-binding sites) could be considered when evaluating the role of TS genotype in the efficacy of the 5-FU-based regimens. Further, confirmatory studies aimed at evaluating the effect of the number of binding sites of transcription factors for selecting 5-FU-treated patients are warranted.
Department of Genetics, Hospital de Santa Creu i Sant Pau. Universitat Autonoma de Barcelona, Barcelona, Spain.
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001665:Binding Sites; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D013940:Thymidylate Synthase / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D014157:Transcription Factors; D000077150:Oxaliplatin; D013940:Thymidylate Synthase; D005472:Fluorouracil