Thymidylate Synthase 31 UTR 6bp Deletion

A third polymorphism of the TS gene is a 6bp deletion in the 3'-UTR region of the gene (Fig. 3). This polymorphism was identified by aligning expressed sequence tag (EST) databases (61). The deletion occurs at an allele frequency of 27%-29% in Caucasians (+6bp/+6bp, 48%; +6bp/-6bp, 44%; -6bp/-6bp, 7%) (61,62). The authors proposed that alterations in the 3'-UTR region of the TS gene could alter RNA stability and therefore influence TS mRNA and TS protein expression (61).

Preliminary data from 43 patients analyzed for TS mRNA expression and 3'-UTR 6bp deletion suggest that patients homozygous for 6bp deletion (-6bp/-6bp) express threefold less TS mRNA than patients homozygous for the presence of the 6bp (+6bp/+6bp) (p = 0.017) (42,59,62). A recent study by Dotor et al. illustrated that in series of ho-mogenously 5-FU treated patients, the presence of homozygous 3'-UTR 6bp deletion (-6bp/-6bp) appears to be a strong prognostic factor, which may be of benefit for at least 20% of the study population (63).

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