The relationship between 5-fluorouracil sensitivity and single nucleotide polymorphisms of the orotate phosphoribosyl transferase gene in colorectal cancer.

Orotate phosphoribosyl transferase (OPRT) is an enzyme playing an important role in exertion of the effect of 5-fluorouracil (5-FU). A type of gene polymorphism, single nucleotide polymorphism (SNP), is considered to be a factor affecting individual differences in exertion of drug effects, and its analysis has recently made progress. We investigated the correlation between SNP of OPRT and 5-FU sensitivity in colon and rectal cancers. The subjects were 31 patients with colorectal cancer who underwent surgical excision between December 2003 and July 2004 at our department. Of SNP of OPRT, 638G/C, 1050T/A, and 1336A/G located in the coding region were analyzed by invader assay. The growth inhibition rate (% IR) of colorectal cancer by 5-FU was obtained by the CDDST method, and 5-FU sensitivity was compared among strains (wild-, homo-, and hetero-types) of each polymorphism. There was no relationship between the strains and 5-FU sensitivity in any of the SNPs. The investigated SNPs of OPRT may have no major influence on 5-FU sensitivity. However, there are many unknown factors in the relationship between SNP of OPRT and 5-FU sensitivity, and SNP analysis of other regions is necessary.