Tumor Biology

, Volume 36, Issue 8, pp 5831–5837 | Cite as

Differential expression of the UGT1A family of genes in stomach cancer tissues

  • Beyhan Cengiz
  • Onder Yumrutas
  • Esra Bozgeyik
  • Ersin Borazan
  • Yusuf Ziya Igci
  • Ibrahim Bozgeyik
  • Serdar Oztuzcu
Research Article


Uridine 5′-diphospho-glucuronosyltransferases (UGT) are the key players in the biotransformation of drugs, xenobiotics, and endogenous compounds. Particularly, UDP-glucuronosyltransferase 1A (UGT1A) participates in a wide range of biological and pharmacological processes and plays a critical role in the conjugation of endogenous and exogenous components. Thirteen alternative splicing products were produced from UGT1A gene locus designated as UGT1A1 and UGT1A3–10. A growing amount of evidence suggests that they have important roles in the carcinogenesis which is well documented by colon, liver, pancreas, and kidney cancer studies. Here, we report differential expressions of UGT1A genes in normal and tumor tissues of stomach cancer patients. Total numbers of 49 patients were enrolled for this study, and expression analysis of UGT1A genes was evaluated by the real-time PCR method. Accordingly, UGT1A1, UGT1A8, and UGT1A10 were found to be upregulated, and UGT1A3, UGT1A5, UGT1A7, and UGT1A9 were downregulated in stomach tumors. No expression changes were observed in UGT1A4. Also, UGT1A6 transcription variants were significantly upregulated in stomach cancer tissues compared to normal stomach tissue. Additionally, UGT1A7 gene showed highest expression in both normal and tumoral tissues, and interestingly, UGT1A7 gene expression was significantly reduced in stage II patients as compared to other patients. In conclusion, UGT1A genes are differentially expressed in normal and tumoral stomach tissues and expression changes of these genes may affect the development and progression of various types of cancer including the cancer of the stomach.


Gene expression Stomach cancer UDP-glucuronosyltransferases UGT1A UGT1A6 


Conflicts of interest


Supplementary material

13277_2015_3253_MOESM1_ESM.docx (22 kb)
Supplementary Table 1 (DOCX 22 kb)
13277_2015_3253_MOESM2_ESM.docx (26 kb)
Supplementary Table 2 (DOCX 26 kb)


  1. 1.
    Levesque E, Girard H, Journault K, Lepine J, Guillemette C. Regulation of the UGT1A1 bilirubin‐conjugating pathway: role of a new splicing event at the UGT1A locus. Hepatology. 2007;45:128–38.CrossRefPubMedGoogle Scholar
  2. 2.
    Mackenzie PI, Rodbourne L, Stranks S. Steroid UDP glucuronosyltransferases. J Steroid Biochem Mol Biol. 1992;43:1099–105.CrossRefPubMedGoogle Scholar
  3. 3.
    Wilson ID, Nicholson JK. Topics in xenobiochemistry: do metabolic pathways exist for xenobiotics? The micro-metabolism hypothesis. Xenobiotica. 2003;33:887–901.CrossRefPubMedGoogle Scholar
  4. 4.
    Miners JO, Mackenzie PI. Drug glucuronidation in humans. Pharmacol Ther. 1991;51:347–69.CrossRefPubMedGoogle Scholar
  5. 5.
    Belanger A, Pelletier G, Labrie F, Barbier O, Chouinard S. Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol Metab. 2003;14:473–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Owens IS, Ritter JK, Yeatman MT, Chen F. The novel UGT1 gene complex links bilirubin, xenobiotics, and therapeutic drug metabolism by encoding UDP-glucuronosyltransferase isozymes with a common carboxyl terminus. J Pharmacokinet Biopharm. 1996;24:491–508.CrossRefPubMedGoogle Scholar
  7. 7.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.CrossRefPubMedGoogle Scholar
  8. 8.
    Bigler J, Whitton J, Lampe JW, Fosdick L, Bostick RM, Potter JD. CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res. 2001;61:3566–9.PubMedGoogle Scholar
  9. 9.
    Piepoli A, Gentile A, Valvano MR, Barana D, Oliani C, Cotugno R, et al. Lack of association between UGT1A7, UGT1A9, ARP, SPINK1 and CFTR gene polymorphisms and pancreatic cancer in Italian patients. World J Gastroenterol. 2006;12:6343.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Strassburg CP, Nguyen N, Manns MP, Tukey RH. Polymorphic expression of the UDP-glucuronosyltransferase UGT1A gene locus in human gastric epithelium. Mol Pharmacol. 1998;54:647–54.PubMedGoogle Scholar
  11. 11.
    Tseng C-S, Tang K-S, Lo H-W, Ker C-G, Teng H-C, Huang C-S. UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma risk and onset age. Am J Gastroenterol. 2005;100:1758.CrossRefPubMedGoogle Scholar
  12. 12.
    Rouleau M, Roberge J, Bellemare J, Guillemette C. Dual roles for splice variants of the glucuronidation pathway as regulators of cellular metabolism. Mol Pharmacol. 2014;85:29–36.CrossRefPubMedGoogle Scholar
  13. 13.
    Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3:1101–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Strassburg CP, Kalthoff S, Ehmer U. Variability and function of family 1 uridine-5′-diphosphate glucuronosyltransferases (UGT1A). Crit Rev Clin Lab Sci. 2008;45:485–530.CrossRefPubMedGoogle Scholar
  15. 15.
    Strassburg CP, Manns MP, Tukey RH. Expression of the UDP-glucuronosyltransferase 1A locus in human colon identification and characterization of the novel extrahepatic UGT1A8. J Biol Chem. 1998;273:8719–26.CrossRefPubMedGoogle Scholar
  16. 16.
    Strassburg CP, Oldhafer K, Manns MP, Tukey RH. Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: Identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue. Mol Pharmacol. 1997;52:212–20.PubMedGoogle Scholar
  17. 17.
    Wang M, Sun D-F, Wang S, Qing Y, Chen S, Wu D, et al. Polymorphic expression of UDP-glucuronosyltransferase UGTlA gene in human colorectal cancer. PLoS One. 2013;8:e57045.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Nakamura A, Nakajima M, Yamanaka H, Fujiwara R, Yokoi T. Expression of UGT1A and UGT2B mRNA in human normal tissues and various cell lines. Drug Metab Dispos. 2008;36:1461–4.CrossRefPubMedGoogle Scholar
  19. 19.
    Finel M, Li X, Gardner-Stephen D, Bratton S, Mackenzie PI, Radominska-Pandya A. Human UDP-glucuronosyltransferase 1A5: identification, expression, and activity. J Pharmacol Exp Ther. 2005;315:1143–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Osawa K, Nakarai C, Akiyama M, Hashimoto R, Tsutou A, Takahashi J, et al. Association between polymorphisms in UDP-glucuronosyltransferase 1A6 and 1A7 and colorectal cancer risk. Asian Pac J cancer Prev. 2012;5:2311–4.CrossRefGoogle Scholar
  21. 21.
    Girard H, Levesque E, Bellemare J, Journault K, Caillier B, Guillemette C. Genetic diversity at the UGT1 locus is amplified by a novel 3′ alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity. Pharmacogenet Genomics. 2007;17:1077–89.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Beyhan Cengiz
    • 1
  • Onder Yumrutas
    • 2
  • Esra Bozgeyik
    • 3
  • Ersin Borazan
    • 4
  • Yusuf Ziya Igci
    • 3
  • Ibrahim Bozgeyik
    • 2
  • Serdar Oztuzcu
    • 3
  1. 1.Department of Medical Biology, Faculty of MedicineGazi UniversityAnkaraTurkey
  2. 2.Department of Medical Biology, Faculty of MedicineAdiyaman UniversityAdiyamanTurkey
  3. 3.Department of Medical Biology, Faculty of MedicineGaziantep UniversityGaziantepTurkey
  4. 4.Department of General Surgery, Faculty of MedicineGaziantep UniversityGaziantepTurkey

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