Functional Polymorphism of the Thymidylate Synthase Gene in Colorectal Cancer Accompanied by Frequent Loss of Heterozygosity

摘要: The thymidylate synthase (TS) gene has a polymorphic repeated sequence in its 5′-untranslated region. repeat length is associated with TS protein expression, which suggests that we may be able to predict the efficacy of 5-fluorouracil (S-FU)-based chemotherapy from patient's genotype determined through analysis normal tissue obtained non-invasively. However, it not yet elucidated whether identical tumor and tissue. In this study, investigated 151 matched DNA samples isolated colorectal cancer adjacent tissues by PCR analysis. results showed genotypes are homozygous individuals, suggesting stable carcinogenesis. heterozygous samples, an unbalance between 2R 3R alleles was frequently observed, loss heterozygosity (LOH) at locus. Detailed LOH revealed 62% (31 50) 2R/3R-heterozygous had LOH. Frequent locus confirmed RT-PCR mRNA microsatellite using marker D18S59, located on 18p11.3. There no difference expressions non-LOH samples. when bearing subdivided according number repeats, 2R/loss expressed significantly lower level than did 3R/loss genotype. suggest due should considered analyzed tissue, such as peripheral blood cells, because important for expression.