5-FU is the most widely used anticancer
drug for
digestive system cancers, and it has been recently reported that the effect of
5-FU varies with the amount of
enzymes that are involved in the
drug metabolism in the
cancer tissue. In this report, we measured DPD and OPRT activities in the normal mucosa and
colorectal cancer tissues and compared them with clinicopathological factors to examine the choice of
chemotherapy for
colorectal cancers. Forty-six patients with
colorectal carcinoma (28 colon and 18
rectal cancers), which were resected in our department from 1999 to March 2003, were examined. There was no significant difference in the DPD activities between the normal and
cancer tissues, whereas OPRT showed significantly higher activity in the
cancer tissues. Although we did not find a relation between the DPD activity and clinicopathological factors, the OPRT activity showed a significant difference between gender and classification of
tumor, and
mucinous adenocarcinoma showed significantly lower OPRT activity than differentiated
adenocarcinoma. The DPD activity of
mucinous adenocarcinoma is related to catabolism of
5-FU is equal to that of
adenocarcinoma, however, the OPRT activity is related to a main pathway of
5-FU phosphorylation is significantly lower. Thus,
mucinous adenocarcinoma of the colon was more resistant to
5-FU than the differentiated
adenocarcinoma. Therefore, for
chemotherapy of
mucinous adenocarcinoma,
anticancer agents other than
5-FU should be selected.