1. ¹Oncology Unit, Rovigo Hospital, Rovigo, Italy
2. ²Department of Pharmacology and Anesthesiology, University of Padova, Padova, Italy

Correspondence: Dr M Gusella, Unità Operativa di Oncologia, Ospedale Civile di Rovigo, Viale Tre Martiri, 140, Rovigo 45100, Italy. E-mail: gusella.milena@azisanrovigo.it

Received 11 January 2006; Revised 28 March 2006; Accepted 2 May 2006; Published online 25 July 2006.

Abstract

Thymidylate synthase (TYMS) is the main molecular target for fluoropyrimidine anticancer drugs, and its expression has been correlated with the number of repeats of a 28-bp sequence in the 5'-untranslated region of the TYMS gene and with the presence of a G C single-nucleotide polymorphism in the second repeat of 3R alleles. Based on this double polymorphism, three main TYMS alleles have so far been identified: TYMS 2R, TYMS 3RC and TYMS 3RG. During genetic analysis of TYMS polymorphisms in 100 colorectal cancer patients, three patients revealed an unexpected 113-bp band after electrophoresis of the restriction fragment length polymorphism analysis. Subsequent sequencing revealed two 28-bp repeats in the 5'-untranslated region and the presence in both repeats of cytosine instead of guanine at the 12th nucleotide. This allele variant (TYMS 2RC) has not been previously described in man. All three patients were heterozygotes for TYMS 2RC and experienced grade 2–3 chemotherapy-related toxicity.