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

  • Epidemiology
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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.

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Acknowledgements

The authors wish to thank all of the family members who have participated in the Metropolitan New York Registry. This research was supported by the National Cancer Institute, National Institutes of Health under RFA CA-95-011 and through cooperative agreements with members of the Breast Cancer Family Registry, the National Cancer Institute (U01 CA069398, P30 CA013696, R25 CA09406), the National Institute of Environmental Health Sciences (P30 ES09089), and the US Department of Defense (DAMD17-00-1-0213, DAMD17-02-1-0354). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute, the National Institute of Environmental Health Sciences, or any of the collaborating centers in the CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR.

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Correspondence to Heather Greenlee.

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Greenlee, H., Chen, Y., Kabat, G.C. et al. Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer. Breast Cancer Res Treat 102, 111–117 (2007). https://doi.org/10.1007/s10549-006-9308-7

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  • DOI: https://doi.org/10.1007/s10549-006-9308-7

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