title: Association of estrogen receptor and glucocorticoid receptor gene polymorphisms with sporadic breast cancer.
abstract: We have utilized a cross-sectional association approach to investigate sporadic breast cancer. Polymorphisms in 2 candidate genes, ESRalpha and GRL, were examined in an unrelated breast cancer-affected and age-matched control population. Several polymorphic regions within the ESRalpha gene have been identified, and some alleles of these polymorphisms have been found to occur at increased levels in breast-cancer patients. Additionally, variations in GRL have the potential to disrupt cell transcription and may be associated with cancer formation. We analyzed 3 polymorphisms, from codons 10 (TCT to TCC), 325 (CCC to CCG) and 594 (ACA to ACG) of ESRalpha, and a highly polymorphic dinucleotide repeat, D5S207, located within 200 kb of the GRL. When allelic frequencies of the codon 594 (exon 8) ESR polymorphism were compared between affected and unaffected populations, a significant difference was observed (p = 0.005). Results from the D5S207 dinucleotide repeat located near GRL also indicated a significant difference between the tested case and control populations (p = 0.001). Allelic frequencies of the codon 10 and codon 325 ESR polymorphisms were not significantly different between populations (p = 0.152 and 0.181, respectively). Our results indicate that specific alleles of the ESR gene (alpha subtype) and a marker for the GRL gene locus are associated with sporadic breast-cancer development in the tested Caucasian population and justify further investigation of the role of these and other nuclear steroid receptors in the etiology of breast cancer.
authors.affiliation: Genomics Research Centre, School of Health Science, Griffith University Gold Coast, Southport, Queensland, Australia.
authors.forename: J E
authors.initials: JE
authors.lastname: Curran
authors.forename: R A
authors.initials: RA
authors.lastname: Lea
authors.forename: S
authors.initials: S
authors.lastname: Rutherford
authors.forename: S R
authors.initials: SR
authors.lastname: Weinstein
authors.forename: L R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D008875:Middle Aged; D009010:Monte Carlo Method; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012306:Risk
chemical_list: D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid