Gender differences in the dihydropyrimidine dehydrogenase expression of colorectal cancers.
Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). DPD expression levels are believed to correlate with the 5-FU sensitivity of malignant tumors. In colorectal cancer (CRC), a few previous studies demonstrated that females could benefit more from adjuvant chemotherapy. However, it is still unknown why the effectiveness of postoperative chemotherapy is affected by gender. The objective of this study was to clarify the beneficial differences in 5-FU chemotherapy between genders in patients with the CRC based on DPD expression. Ninety-seven tumor specimens and 92 adjacent normal tissue specimens from 97 patients with the CRC and no prior therapy were obtained. The DPD expression in the tissues was quantified and analyzed based on clinicopathological factors. In the tumor tissue, the DPD expression in females was significantly lower than that in males. In the normal tissues, however, there were no significant differences in DPD expression between genders. In the treatment of CRC, cases who will benefit most because of 5-FU sensitivity; i.e. cases with lower DPD expression, must be given priority. Based on DPD expression, female gender seems to be a predictive factor for a better response to chemotherapy with 5-FU.
Yamashita
Kazuki
K
Department of Surgery, Division of Gastroenterology, Kawasaki Medical School, 577, 701-0192, Matsushima Kurashiki City, Japan. kazuki@med.kawasaki-m.ac.jp
Mikami
Yoshiko
Y
Ikeda
Masaharu
M
Yamamura
Masahiko
M
Kubozoe
Tadahiko
T
Urakami
Atsushi
A
Yoshida
Kazuhiro
K
Kimoto
Masatoshi
M
Tsunoda
Tsukasa
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000201:enzymology / Q000556:secondary; D012727:Sex Characteristics
D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil