Breast Cancer Research and Treatment

, Volume 122, Issue 3, pp 879–882 | Cite as

The association between TA-repeat polymorphism in the promoter region of UGT1A1 and breast cancer risk: a meta-analysis

  • Lei Yao
  • Li-Xin Qiu
  • Lu Yu
  • Zhen Yang
  • Xia-Jia Yu
  • Yang Zhong
  • Long Yu


Uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) plays an important role in breast cancer development. To date, many publications have evaluated the correlation between UGT1A1 TA-repeat polymorphism and breast cancer risk. However, the results remain inconclusive. In order to resolve this conflict, a meta-analysis was performed by searching Medline, PubMed, and ISI Web of Knowledge databases. Seven studies including 5,746 cases and 8,365 controls were collected for UGT1A1 TA-repeat polymorphism. The strength of association between UGT1A1 TA-repeat polymorphism and breast cancer risk was assessed by calculating crude ORs with 95% CIs. Overall, no significant associations between UGT1A1 TA-repeat polymorphism and breast cancer susceptibility were found. In the stratified analysis by ethnicity and source of controls, significant associations were only observed for 6/6 versus 7/7 (OR = 0.88; 95% CI: 0.77–0.99; P = 0.425 for heterogeneity) in Caucasians, but no in other genetic models. In conclusion, this meta-analysis suggests that UGT1A1 A(TA)7TAA allele is a potential risk factor for breast cancer in Caucasians.


UGT1A1 Polymorphism Breast cancer Meta-analysis 



This study was supported by national 973 programs of China grants 2004CB518605, the national 863 project of China grants 2006AA020501, and the national key sci-tech special project of China grants 2008ZX10002-020.


  1. 1.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249CrossRefPubMedGoogle Scholar
  2. 2.
    Cheng Z, Rios GR, King CD, Coffman BL, Green MD, Mojarrabi B, Mackenzie PI, Tephly TR (1998) Glucuronidation of catechol estrogens by expressed human UDP-glucuronosyltransferases (UGTs) 1A1, 1A3, and 2B7. Toxicol Sci 45:52–57PubMedGoogle Scholar
  3. 3.
    Senafi SB, Clarke DJ, Burchell B (1994) Investigation of the substrate specificity of a cloned expressed human bilirubin UDP-glucuronosyltransferase: UDP-sugar specificity and involvement in steroid and xenobiotic glucuronidation. Biochem J 303:233–240PubMedGoogle Scholar
  4. 4.
    Girard H, Thibaudeau J, Court MH, Fortier LC, Villeneuve L, Caron P, Hao Q, von Moltke LL, Greenblatt DJ, Guillemette C (2005) UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver. Hepatology 42:448–457CrossRefPubMedGoogle Scholar
  5. 5.
    Fang JL, Lazarus P (2004) Correlation between the UDP-glucuronosyltransferase (UGT1A1) TATAA box polymorphism and carcinogen detoxification phenotype: significantly decreased glucuronidating activity against benzo(a)pyrene-7,8-dihydrodiol(-) in liver microsomes from subjects with the UGT1A1*28 variant. Cancer Epidemiol Biomark Prev 13:102–109CrossRefGoogle Scholar
  6. 6.
    Gagné JF, Montminy V, Belanger P, Journault K, Gaucher G, Guillemette C (2002) Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Mol Pharmacol 62:608–617CrossRefPubMedGoogle Scholar
  7. 7.
    Schulz C, Boeck S, Heinemann V, Stemmler HJ (2009) UGT1A1 genotyping: a predictor of irinotecan-associated side effects and drug efficacy? Anticancer Drugs 20:867–879CrossRefPubMedGoogle Scholar
  8. 8.
    Yager JD, Davidson NE (2006) Mechanisms of disease: estrogen carcinogenesis in breast cancer. N Engl J Med 354:270–282CrossRefPubMedGoogle Scholar
  9. 9.
    Krajinovic M, Ghadirian P, Richer C, Sinnett H, Gandini S, Perret C, Lacroix A, Labuda D, Sinnett D (2001) Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions. Int J Cancer 92:220–225CrossRefPubMedGoogle Scholar
  10. 10.
    Beutler E, Gelbart T, Demina A (1998) Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci USA 95:8170–8174CrossRefPubMedGoogle Scholar
  11. 11.
    Lampe JW, Bigler J, Horner NK, Potter JD (1999) UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics 9:341–349CrossRefPubMedGoogle Scholar
  12. 12.
    Hall D, Ybazeta G, Destro-Bisol G, Petzl-Erler ML, Di Rienzo A (1999) Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates. Pharmacogenetics 9:591–599CrossRefPubMedGoogle Scholar
  13. 13.
    Duguay Y, McGrath M, Lépine J, Gagné JF, Hankinson SE, Colditz GA, Hunter DJ, Plante M, Têtu B, Bélanger A, Guillemette C, De Vivo I (2004) The functional UGT1A1 promoter polymorphism decreases endometrial cancer risk. Cancer Res 64:1202–1207CrossRefPubMedGoogle Scholar
  14. 14.
    Hsieh TY, Shiu TY, Huang SM, Lin HH, Lee TC, Chen PJ, Chu HC, Chang WK, Jeng KS, Lai MM, Chao YC (2007) Molecular pathogenesis of Gilbert’s syndrome: decreased TATA-binding protein binding affinity of UGT1A1 gene promoter. Pharmacogenet Genomics 17:229–236CrossRefPubMedGoogle Scholar
  15. 15.
    Raijmakers MT, Jansen PL, Steegers EA, Peters WH (2000) Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene. J Hepatol 33:348–351CrossRefPubMedGoogle Scholar
  16. 16.
    Guillemette C, Millikan RC, Newman B, Housman DE (2000) Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African Americans. Cancer Res 60:950–956PubMedGoogle Scholar
  17. 17.
    Guillemette C, De Vivo I, Hankinson SE, Haiman CA, Spiegelman D, Housman DE, Hunter DJ (2001) Association of genetic polymorphisms in UGT1A1 with breast cancer and plasma hormone levels. Cancer Epidemiol Biomark Prev 10:711–714Google Scholar
  18. 18.
    Adegoke OJ, Shu XO, Gao YT, Cai Q, Breyer J, Smith J, Zheng W (2004) Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer. Breast Cancer Res Treat 85:239–245CrossRefPubMedGoogle Scholar
  19. 19.
    Cheng TC, Chen ST, Huang CS, Fu YP, Yu JC, Cheng CW, Wu PE, Shen CY (2005) Breast cancer risk associated with genotype polymorphism of the catechol estrogen-metabolizing genes: a multigenic study on cancer susceptibility. Int J Cancer 113:345–353CrossRefPubMedGoogle Scholar
  20. 20.
    Tsezou A, Tzetis M, Giannatou E, Gennatas C, Pampanos A, Kanavakis E, Kitsiou-Tzeli S (2007) Genetic polymorphisms in the UGT1A1 gene and breast cancer risk in Greek women. Genet Test 11:303–306CrossRefPubMedGoogle Scholar
  21. 21.
    Huo D, Kim HJ, Adebamowo CA, Ogundiran TO, Akang EE, Campbell O, Adenipekun A, Niu Q, Sveen L, Fackenthal JD, Fackenthal DL, Das S, Cox N, Di Rienzo A, Olopade OI (2008) Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and breast cancer risk in Africans. Breast Cancer Res Treat 110:367–376CrossRefPubMedGoogle Scholar
  22. 22.
    MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk (2010) Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women. Breast Cancer Res Treat 119:463–474Google Scholar
  23. 23.
    Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129CrossRefGoogle Scholar
  24. 24.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  25. 25.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMedGoogle Scholar
  26. 26.
    Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  27. 27.
    Kaplan M, Hammerman C, Beutler E (2001) Heterozygosity for a polymorphism in the promoter region of the UGT1A1 gene. J Hepatol 35:148–151CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Lei Yao
    • 1
    • 5
  • Li-Xin Qiu
    • 3
    • 4
  • Lu Yu
    • 1
  • Zhen Yang
    • 5
  • Xia-Jia Yu
    • 1
  • Yang Zhong
    • 5
  • Long Yu
    • 1
    • 2
  1. 1.State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life SciencesFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Institutes of Biomedical SciencesFudan UniversityShanghaiPeople’s Republic of China
  3. 3.Department of Medical Oncology, Cancer HospitalFudan UniversityShanghaiPeople’s Republic of China
  4. 4.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiPeople’s Republic of China
  5. 5.Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life SciencesFudan UniversityShanghaiPeople’s Republic of China

Personalised recommendations