TY - JOUR
T1 - Estrogen receptor genotypes and haplotypes associated with breast cancer risk
AU - Gold, Bert
AU - Kalush, Francis
AU - Bergeron, Julie
AU - Scott, Kevin
AU - Mitra, Nandita
AU - Wilson, Kelly
AU - Ellis, Nathan
AU - Huang, Helen
AU - Chen, Michael
AU - Lippert, Ross
AU - Halldorsson, Bjarni V.
AU - Woodworth, Beth
AU - White, Thomas
AU - Clark, Andrew G.
AU - Parl, Fritz F.
AU - Broder, Samuel
AU - Dean, Michael
AU - Offit, Kenneth
PY - 2004/12/15
Y1 - 2004/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=10844265490&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10844265490&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-04-1256
DO - 10.1158/0008-5472.CAN-04-1256
M3 - Article
C2 - 15604249
AN - SCOPUS:10844265490
SN - 0008-5472
VL - 64
SP - 8891
EP - 8900
JO - Cancer Research
JF - Cancer Research
IS - 24
ER -