title: Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women.
abstract: Life-long exposure to estrogen is an established risk factor for breast cancer development. The underlying mechanism has been suggested to be the binding of estrogen-to-estrogen receptors in mammary tissue, which in turn promotes the proliferation and differentiation of breast tissue. Polymorphisms and haplotypes in estrogen receptor alpha (ESR1) have been reportedly associated with breast cancer risk; however, the results are not fully consistent. In this study, we investigated breast cancer risk associated with genotypes and haplotypes resulting from four ESR1 single nucleotide polymorphisms (SNPs), rs746432, rs2234693, rs9340799, and rs1801132. Genotyping has been performed on 393 breast cancer cases and 790 randomly selected controls in 1,183 Caucasian women over age 65 from the Study of Osteoporotic Fractures (SOF). We observed an allelic protective effect for SNP rs9340799 with an estimated odds ratio (OR) of 0.82 (95% CI = 0.68-1.00; P = 0.04) after adjustment for age, BMI and hip BMD. A protective effect of this SNP has been reported before in several different studies. We did not replicate the previously reported C-C-A-G haplotype association to breast cancer-the C-C-A-G haplotype from these SNPs was rare in this study (estimated frequency below 0.001% in cases and controls). No other statistically significant associations were observed between ESR1 haplotypes from the same four SNPs and the risk of breast cancer in older Caucasian women.
authors.affiliation: Human Genetics Department, Roche Molecular Systems, Inc., 1145 Atlantic Ave, Alameda, CA 94555, USA. jun.wang@roche.com
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Russell
authors.initials: R
authors.lastname: Higuchi
authors.forename: Francesmary
authors.initials: F
authors.lastname: Modugno
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Nanette
authors.initials: N
authors.lastname: Umblas
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Lee
authors.forename: Li-Yung
authors.initials: LY
authors.lastname: Lui
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Tice
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Brian
authors.initials: B
authors.lastname: Rhees
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha