Skip to main content
SpringerLink
Log in

Differences in Dihydropyrimidine Dehydrogenase Activities Between Gastric and Colorectal Cancer

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

We studied the relation between clinicopathological factors and dihydropyrimidine dehydrogenase (DPD) activity in gastric and colorectal carcinomas. Specimens obtained by surgery from 27 gastric and 17 colorectal carcinomas and their normal mucosa were examined. The levels of DPD activity in the gastric carcinomas and their normal mucosa were significantly higher than those in colorectal carcinomas and their normal counterparts, respectively (both P's<0.0001). The gastric carcinomas had significantly higher DPD activities than their normal mucosa (P = 0.028), but the colorectal carcinomas did not. Among the clinicopathological factors, which included invasion/metastatic status and staging, the only effect was that of the histological differences of gastric cancer on DPD activity. That is, the level of DPD activity of the histologically undifferentiated gastric carcinoma was significantly higher than that of the differentiated type. No prognostic predictive values of DPD were recognized in either gastric and colorectal cancer. In conclusion, the higher DPD activity in gastric cancer than colorectal cancer may be due to the higher DPD activity in the background mucosa of origin, and the higher population of undifferentiated type of histological classification, compared to the colorectal counterparts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Nakajima T: Review of adjuvant chemotherapy for gastric cancer. World J Surg 19:570–574, 1995

    Google Scholar 

  2. Macdonald JS: Adjuvant therapy for colon cancer. CA Cancer J Clin 47:243–256, 1997

    Google Scholar 

  3. Diasio RB, Harris BE: Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet 16:215–237, 1989

    Google Scholar 

  4. Rustum YM, Harstrick A, Cao S, Vanhoefer U, Yin MB, Wilke H, Seeber S: Thymidylate synthase inhibitors in cancer therapy: direct and indirect inhibitors. J Clin Oncol 15:389–400, 1997

    Google Scholar 

  5. Etienne MC, Chradame S, Fischel JL, Formento P, Dassonville O, Rene N, Schneider M, Thyss A, Demard F, Milano G: Response to fluorouracil therapy in cancer patients: the role of tumoral dihydropyrimidine dehydrogenase activity. J Clin Oncol 13:1663–1670, 1995

    Google Scholar 

  6. Ishikawa Y, Kubota T, Otani Y, Watanabe M, Teramoto T, Kumai K, Takechi T, Okabe H, Fukushima M, Kitajima M: Dihydropyrimidine dehydrogenase and messenger RNA levels in gastric cancer: possible predictor for sensitivity to 5-fluorouracil. Jpn J Cancer Res91:105–112, 2000

    Google Scholar 

  7. Salonga D, Danenberg KD, Johnson M, Metzger R, Groshen S, Tsao-Wei DD, Lenz HJ, Leichman CG, Leichman L, Diasio RB, Danenberg PV: Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. Clin Cancer Res 6:1322–1327, 2000

    Google Scholar 

  8. Japanese Research Society for Gastric Cancer: Japanese classification of gastric carcinoma, 1st English ed. Tokyo, Kanehara, 1995

    Google Scholar 

  9. International Union Against Cancer: TNM Classification of Malignant Tumours, 5th ed. LH Sobin, Ch Wittekind (eds). New York, Wiley-Liss, 1997

    Google Scholar 

  10. Harris BE, Song R, Soong S, Diasio RB: Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion. Cancer Res 50:197–201, 1990

    Google Scholar 

  11. Sommadossi JP, Gewirtz DA, Diasio RB, Aubert C, Cano JP, Goldman ID: Rapid catabolism of 5-fluorouracil in freshly isolated rat hepatocytes as analyzed by high-performance liquid chromatography. J Biol Chem 257:8171–8176, 1982

    Google Scholar 

  12. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951

    Google Scholar 

  13. Takenoue T, Kitayama J, Takei Y, Umetani N, Matsuda K, Nita ME, Hatano K, Tsuruo T, Nagawa H: Characterization of dihydropyrimidine dehydrogenase on immunohistochemistry in colon carcinoma, and correlation between immunohistochemical score and protein level or messenger RNA expression. Ann Oncol11:273–279, 2000

    Google Scholar 

  14. Naquib FNM, el Kouni MH, Cha S: Enzymes of uracil catabolism in normal and neoplastic human tissues. Cancer Res 45:5405–5412, 1985

    Google Scholar 

  15. Nozawa H, Tsukui H, Nishida K, Yakumaru K, Nagawa H, Sekikawa T: Dihydropyrimidine dehydrogenase expression in preoperative biopsy and surgically resected specimens of gastric carcinoma. Cancer Chemother Pharmacol 49:267–273, 2002

    Google Scholar 

  16. Ishikawa Y, Kubota T, Otani Y, Watanabe M, Teramoto T, Kumai K, Takechi T, Okabe H, Fukushima M, Kitajima M: Thymidylate synthase and dihydropyrimidine dehydrogenase levels in gastric cancer. Anticancer Res 19:5635–5640, 1999

    Google Scholar 

  17. Uetake H, Ichikawa W, Takechi T, Fukushima M, Nihei Z, Sugihara K: Relationship between intratumoral dihydropyrimidine dehydrogenase activity and gene expression in human colorectal cancer. Clin Cancer Res 5:2836–2839, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-5-4 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Bunzo Nakata, Kazuya Muguruma, Shigehito Yamagata, Kiyotaka Yukimoto, Kiyoshi Maeda, Yukio Nishiguchi, Masaichi Ohira, Yasuyuki Kato & Kosei Hirakawa

Authors
  1. Bunzo Nakata
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuya Muguruma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shigehito Yamagata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kiyotaka Yukimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kiyoshi Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yukio Nishiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masaichi Ohira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yasuyuki Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kosei Hirakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakata, B., Muguruma, K., Yamagata, S. et al. Differences in Dihydropyrimidine Dehydrogenase Activities Between Gastric and Colorectal Cancer. Dig Dis Sci 49, 60–64 (2004). https://doi.org/10.1023/B:DDAS.0000011603.40133.f9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:DDAS.0000011603.40133.f9

Search

Navigation