Regular Article

British Journal of Cancer (2001) 85, 827–830. doi:10.1054/bjoc.2001.2007 www.bjcancer.com
Published online 11 September 2001

A polymorphism in the enhancer region of the thymidylate synthase promoter influences the survival of colorectal cancer patients treated with 5-fluorouracil

B Iacopetta1, F Grieu2, D Joseph2,3 and H Elsaleh1,2

  1. 1Department of Surgery, University of Western Australia, Nedlands 6907, Australia
  2. 2Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands 6009, Australia
  3. 3Department of Medicine, University of Western Australia, Nedlands 6907, Australia

Received 26 October 2000; Revised 21 June 2001; Accepted 3 July 2001.

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Abstract

High levels of thymidylate synthase (TS) expression have been associated with poor survival of colorectal cancer (CRC) patients to 5-fluorouracil (5-FU)-based chemotherapy. Recent evidence suggests that a polymorphism within the enhancer region of the TS gene promoter can influence TS expression, with the triple repeat homozygote (3R/3R) being associated with significantly higher tumour TS levels than either the double repeat homozygote (2R/2R) or heterozygotes (2R/3R). In the present study we investigated whether TS genotype was associated with the degree of survival benefit from chemotherapy in 221 Dukes' C stage CRC patients. Patients with the 3R/3R polymorphism (n = 58, 26%) showed no significant long-term survival benefit from chemotherapy (RR = 0.62, 95% CI: 0.30–1.25, P = 0.18), whereas those with the 2R/2R or 2R/3R genotype (n = 163, 74%) showed significant gains in survival from this treatment (RR = 0.52, 95% CI: 0.52–0.82, P = 0.005). These results demonstrate that a polymorphism within the TS gene, probably through its effect on TS expression levels, can influence the survival benefit obtained by CRC patients from 5-FU-based chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords:

colorectal cancer, adjuvant chemotherapy, thymidylate synthase, polymorphism

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