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. 2001 Sep 14;85(6):827-30. doi: 10.1054/bjoc.2001.2007.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / mortality*
  • DNA Primers / chemistry
  • DNA, Neoplasm / analysis
  • Enhancer Elements, Genetic / genetics*
  • Female
  • Fluorouracil / therapeutic use*
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Survival Rate
  • Tandem Repeat Sequences / genetics
  • Thymidylate Synthase / genetics*


  • Antimetabolites, Antineoplastic
  • DNA Primers
  • DNA, Neoplasm
  • Thymidylate Synthase
  • Fluorouracil