Breast Cancer Research and Treatment

, Volume 102, Issue 1, pp 111–117

Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer

  • Heather Greenlee
  • Yu Chen
  • Geoffrey C. Kabat
  • Qiao Wang
  • Muhammad G. Kibriya
  • Irina Gurvich
  • Daniel W. Sepkovic
  • H. Leon Bradlow
  • Ruby T. Senie
  • Regina M. Santella
  • Habibul Ahsan
Epidemiology

DOI: 10.1007/s10549-006-9308-7

Cite this article as:
Greenlee, H., Chen, Y., Kabat, G.C. et al. Breast Cancer Res Treat (2007) 102: 111. doi:10.1007/s10549-006-9308-7
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Abstract

We examined associations between polymorphisms in genes related to estrogen metabolism (CYP1B1 codon 432G → C rs#1056836, CYP1B1 codon 453A → G rs#1800440, COMT codon 158G → A rs#4680) and biosynthesis (CYP17 T → C promoter rs#743572, CYP19 exon 4 TTTA repeat) and urinary estrogen metabolites (2-hydroxyestrogens (2-OHE), 16α-hydroxyestrone (16α-OHE1), and their ratio) in a pilot study of 64 pre- and post-menopausal women with a family history of breast cancer. Women were participants in the Metropolitan New York Registry of Breast Cancer Families, one of six international sites of the National Cancer Institute’s Breast Cancer Family Registry. We used linear regression to examine the effects of genetic variants on log-transformed urinary estrogen metabolites. After adjusting for menopausal status, BMI, and age, carriers of the CYP1B1 codon 453G variant allele had 31.0% lower levels of 2-OHE (P-value = 0.05) and 40.2% lower levels of 16α-OHE1 (P = 0.01). Results were similar after restricting the analyses to pre-menopausal women (n = 41). Consistent with other studies, among pre-menopausal women, carriers of the COMT codon 158A variant allele had increased 2-OHE levels (P = 0.03) and an increased 2-OHE/16α-OHE1 ratio (P = 0.04); carriers of the CYP17 C promoter variant allele had increased 2-OHE levels (P = 0.08). To our knowledge this is the first report showing associations between the CYP1B1 codon 453G variant allele and urinary 2-OHE and 16α-OHE1 metabolites. Further larger studies should be conducted to confirm these results. Future identification of individuals with genetic polymorphisms that affect estrogen metabolism and biosynthesis may help characterize women at higher breast cancer risk and could guide breast cancer prevention strategies for those individuals.

Keywords

Breast cancer Polymorphisms related to estrogen biosynthesis/metabolism Urinary estrogen metabolites 2-Hydroxyestrogens 16α-Hydroxyestrone 

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Heather Greenlee
    • 1
  • Yu Chen
    • 2
  • Geoffrey C. Kabat
    • 3
  • Qiao Wang
    • 4
  • Muhammad G. Kibriya
    • 1
  • Irina Gurvich
    • 4
  • Daniel W. Sepkovic
    • 5
  • H. Leon Bradlow
    • 5
  • Ruby T. Senie
    • 1
    • 6
  • Regina M. Santella
    • 4
    • 6
  • Habibul Ahsan
    • 1
    • 4
    • 6
  1. 1.Department of Epidemiology, Mailman School of Public HealthColumbia UniversityNew YorkUSA
  2. 2.Department of Environmental MedicineNYU School of MedicineNew YorkUSA
  3. 3.New RochelleNew YorkUSA
  4. 4.Department of Environmental Health Sciences, Mailman School of Public HealthColumbia UniversityNew YorkUSA
  5. 5.Alice and David Jurist Institute for ResearchHackensack University Medical CenterHackensackUSA
  6. 6.Herbert Irving Comprehensive Cancer CenterColumbia UniversityNew YorkUSA

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