Estrogen receptor genotypes and haplotypes associated with breast cancer risk Journal Article
| Authors: | Gold, B.; Kalush, F.; Bergeron, J.; Scott, K.; Mitra, N.; Wilson, K.; Ellis, N.; Huang, H.; Chen, M.; Lippert, R.; Halldorsson, B. V.; Woodworth, B.; White, T.; Clark, A. G.; Parl, F. F.; Broder, S.; Dean, M.; Offit, K. |
| Article Title: | 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), ≃ 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 ≃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. |
| Keywords: | adult; controlled study; middle aged; major clinical study; single nucleotide polymorphism; case-control studies; polymorphism, single nucleotide; cancer risk; united states; reproducibility of results; cancer susceptibility; genetic predisposition to disease; breast cancer; genetic association; genetic variability; genotype; haplotypes; linkage disequilibrium; breast neoplasms; haplotype; cell transformation, neoplastic; base sequence; receptors, progesterone; estrogen receptor; progesterone receptor; postmenopause; genetic epidemiology; ethnic groups; gene replication; estrogen receptor alpha; estrogen receptor beta; humans; human; male; female; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 64 |
| Issue: | 24 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-12-15 |
| Start Page: | 8891 |
| End Page: | 8900 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-04-1256 |
| PROVIDER: | scopus |
| PUBMED: | 15604249 |
| DOI/URL: | |
| Notes: | Cancer Res. -- Cited By (since 1996):79 -- Export Date: 16 June 2014 -- CODEN: CNREA -- Source: Scopus |
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