title: Association of breast cancer risk with a GT dinucleotide repeat polymorphism upstream of the estrogen receptor-alpha gene.
abstract: Recent studies suggest that genetic polymorphisms of the estrogen receptor-alpha (ER-alpha) gene may be associated with breast cancer risk. To evaluate the role of this gene in the risk of breast cancer, we genotyped a newly identified GT dinucleotide repeat [(GT)(n)] polymorphism located in the promoter region (6.6 kb upstream of the transcription start site) in 947 breast cancer cases and 993 age frequency-matched community controls from a population-based case-control study conducted among Chinese in urban Shanghai. Sixteen alleles were identified, the most common one having 16 GT repeats [(GT)(16)]. Compared with subjects homozygous for this allele, subjects carrying the (GT)(17) or (GT)(18) allele had a decreased risk of breast cancer. The odds ratios (ORs) were 0.81 [95% confidence interval (CI), 0.62-1.06] and 0.58 (95% CI, 0.36-0.94), respectively, for one and two copies of the (GT)(17) or (GT)(18) allele. The inverse association with carrying either of these alleles was stronger among women with >30 years of menstrual cycles (OR 0.66; 95% CI 0.51-0.85) than those with a shorter duration of menstrual cycles (OR 0.97; 95% CI 0.73-1.27), and the test for an interaction was statistically significant (P = 0.04). Among breast cancer patients, the presence of either the (GT)(17) or (GT)(18) allele was associated with a reduced expression of progesterone receptor. Results of this study indicate that the GT dinucleotide repeat polymorphism in ER-alpha gene promoter region may be a new biomarker for genetic susceptibility to breast cancer.
authors.affiliation: Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232, USA. qiuyin.cai@vanderbilt.edu
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Wanqing
authors.initials: W
authors.lastname: Wen
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Fan
authors.initials: F
authors.lastname: Jin
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Smith
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D018900:Dinucleotide Repeats / Q000235:genetics*; D047628:Estrogen Receptor alpha; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D011980:Receptors, Progesterone / Q000096:biosynthesis
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone