Breast Cancer Research and Treatment

, Volume 110, Issue 2, pp 367–376

Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and breast cancer risk in Africans

  • Dezheng Huo
  • Hee-Jin Kim
  • Clement A. Adebamowo
  • Temidayo O. Ogundiran
  • Effiong E. Akang
  • Oladapo Campbell
  • Adeniyi Adenipekun
  • Qun Niu
  • Lise Sveen
  • James D. Fackenthal
  • Donna Lee Fackenthal
  • Soma Das
  • Nancy Cox
  • Anna Di Rienzo
  • Olufunmilayo I. Olopade
Epidemiology

DOI: 10.1007/s10549-007-9720-7

Cite this article as:
Huo, D., Kim, H., Adebamowo, C.A. et al. Breast Cancer Res Treat (2008) 110: 367. doi:10.1007/s10549-007-9720-7

Abstract

The UDP-glucuronosylatransferase 1A1 (UGT1A1) gene is involved in the metabolism of estrogen and detoxification of potential carcinogens. The number of TA repeats in the promoter region of UGT1A1 has been linked to breast cancer risk, but results varied by race. We performed a comprehensive assessment of genetic polymorphisms in the UGT1A1 gene, and examined these polymorphisms and TA repeats in relation to breast cancer risk in a case-control study in Nigeria. 512 breast cancer cases and 226 community controls were genotyped for UGT1A1. Compared with high-activity TA repeat genotypes, the odds ratios (OR) for low-activity and moderate-activity genotypes were 0.47 (95% confidence interval CI, 0.26–0.83) and 0.64 (95% CI, 0.39–1.06), respectively, in premenopausal women (P = 0.009 for trend), but no association was observed in postmenopausal women (P = 0.24). The effect of TA repeats was also differentiated by age: the OR was 0.39 (95% CI 0.21–0.71) for low-activity genotypes and 0.58 (95% CI 0.33–1.00) for moderate-activity genotypes in women <45 years old (P = 0.002 for trend), but no association was observed in women ≥45 years old (P = 0.15). Haplotype analysis showed that UGT1A1 haplotypes were highly diverse with blocked structures. We found a specific haplotype in block 2 that was significantly associated with a 2.1-fold elevated risk (95% CI 1.05–4.39; P = 0.04). In contrast with previous studies, we found low-activity TA repeat alleles were protective against breast cancer among premenopausal indigenous Africans, suggesting that the role of UGT1A1 in breast cancer development may vary by population, presumably due to different environmental and genetic modifier effects.

Keywords

AfricanBreast cancerCase-control studyGenetic susceptibilityUGT1A1

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Dezheng Huo
    • 1
  • Hee-Jin Kim
    • 2
  • Clement A. Adebamowo
    • 3
  • Temidayo O. Ogundiran
    • 3
  • Effiong E. Akang
    • 4
  • Oladapo Campbell
    • 5
  • Adeniyi Adenipekun
    • 5
  • Qun Niu
    • 6
  • Lise Sveen
    • 6
  • James D. Fackenthal
    • 6
  • Donna Lee Fackenthal
    • 7
  • Soma Das
    • 7
  • Nancy Cox
    • 8
  • Anna Di Rienzo
    • 7
  • Olufunmilayo I. Olopade
    • 6
    • 7
  1. 1.Department of Health StudiesUniversity of ChicagoChicagoUSA
  2. 2.Department of Laboratory Medicine & Genetics, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  3. 3.Department of SurgeryUniversity of Ibadan and University College HospitalIbadanNigeria
  4. 4.Department of PathologyUniversity of Ibadan and University College HospitalIbadanNigeria
  5. 5.Department of RadiotherapyUniversity of Ibadan and University College HospitalIbadanNigeria
  6. 6.Department of Medicine, Section of Hematology/OncologyUniversity of ChicagoChicagoUSA
  7. 7.Department of Human GeneticsUniversity of ChicagoChicagoUSA
  8. 8.Department of Medicine, Section of Genetic MedicineUniversity of ChicagoChicagoUSA