Estrogen receptor genotypes and haplotypes associated with breast cancer risk.

Abstract

Nearly one in eight US women will develop breast cancer in their lifetime. Most breast cancer is not associated with a hereditary syndrome, occurs in postmenopausal women, and is estrogen and progesterone receptor-positive. Estrogen exposure is an epidemiologic risk factor for breast cancer and estrogen is a potent mammary mitogen. We studied single nucleotide polymorphisms (SNPs) in estrogen receptors in 615 healthy subjects and 1011 individuals with histologically confirmed breast cancer, all from New York City. We analyzed 13 SNPs in the progesterone receptor gene (PGR), 17 SNPs in estrogen receptor 1 gene (ESR1), and 8 SNPs in the estrogen receptor 2 gene (ESR2). We observed three common haplotypes in ESR1 that were associated with a decreased risk for breast cancer [odds ratio (OR), approximately O.4; 95% confidence interval (CI), 0.2-0.8; P < 0.01]. Another haplotype was associated with an increased risk of breast cancer (OR, 2.1; 95% CI, 1.2-3.8; P < 0.05). A unique risk haplotype was present in approximately 7% of older Ashkenazi Jewish study subjects (OR, 1.7; 95% CI, 1.2-2.4; P < 0.003). We narrowed the ESR1 risk haplotypes to the promoter region and first exon. We define several other haplotypes in Ashkenazi Jews in both ESR1 and ESR2 that may elevate susceptibility to breast cancer. In contrast, we found no association between any PGR variant or haplotype and breast cancer. Genetic epidemiology study replication and functional assays of the haplotypes should permit a better understanding of the role of steroid receptor genetic variants and breast cancer risk.

• Authors: Bert Gold, Francis Kalush, Julie Bergeron, Kevin Scott, Nandita Mitra, Kelly Wilson, Nathan Ellis, Helen Huang, Michael Chen, Ross Lippert, Bjarni V Halldorsson, Beth Woodworth, Thomas White, Andrew G Clark, Fritz F Parl, Samuel Broder, Michael Dean, Kenneth Offit
• Journal: Cancer research (Cancer Res) Vol. 64 Issue 24 Pg. 8891-900 (Dec 15 2004) ISSN: 0008-5472 [Print] United States
• PMID: 15604249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Estrogen Receptor alpha
• Estrogen Receptor beta
• Receptors, Progesterone

Topics

• Base Sequence
• Breast Neoplasms (genetics)
• Case-Control Studies
• Cell Transformation, Neoplastic (genetics)
• Estrogen Receptor alpha (genetics)
• Estrogen Receptor beta (genetics)
• Ethnicity (genetics)
• Female
• Genetic Predisposition to Disease
• Genotype
• Haplotypes
• Humans
• Linkage Disequilibrium
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Receptors, Progesterone (genetics)
• Reproducibility of Results