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

British Journal of Cancer volume 85, pages 827–830 (2001)Cite this article

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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

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    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

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Affiliations

  1. Department of Surgery, University of Western Australia, Nedlands, 6907, Australia

    B Iacopetta & H Elsaleh

  2. Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, 6009, Australia

    F Grieu, D Joseph & H Elsaleh

  3. Department of Medicine, University of Western Australia, Nedlands, 6907, Australia

    D Joseph

Authors
  1. B Iacopetta
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  2. F Grieu
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  3. D Joseph
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  4. H Elsaleh
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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Iacopetta, B., Grieu, F., Joseph, D. et al. A polymorphism in the enhancer region of the thymidylate synthase promoter influences the survival of colorectal cancer patients treated with 5-fluorouracil. Br J Cancer 85, 827–830 (2001). https://doi.org/10.1054/bjoc.2001.2007

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Keywords

  • colorectal cancer
  • adjuvant chemotherapy
  • thymidylate synthase
  • polymorphism

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