title: The AIB1 gene polyglutamine repeat length polymorphism contributes to risk of epithelial ovarian cancer risk: a case-control study.
abstract: Genes coding for proteins involved in steroid hormone signaling have been identified as ovarian cancer risk-modifier candidates. AIB1 gene (amplified in breast cancer-1), an androgen receptor (AR) coactivator, expresses a polyglutamine (poly-Q) sequence within the carboxyl-terminal coding region. We hypothesized that genotypic variations in the androgen-signaling pathway promote aggressive epithelial ovarian cancer biology and sought to examine the effect of AIB1 poly-Q repeat length on ovarian cancer risk with a case-control study. The genotype analysis of the AIB1 poly-Q repeat was conducted in 3,000 epithelial ovarian cancer (EOC) cases and 3,000 healthy controls. When analyzed as a categorical variable with cutoff of <28 or <29, both of results showed significant asociations. Compared to those with the shorter (<29) AIB1 poly-Q repeat length, women in the category of longer (≥29) poly-Q repeats had a significantly 20 % increased EOC risk (odds ratio (OR) = 1.20; 95 % confidence interval (CI), 1.08-1.33; P = 5.88 × 10(-4)). When analyzed as a continuous covariate, women with longer average poly-Q repeat length had a significantly increased risk of developing EOC (OR = 1.05 for per poly-Q repeat; 95 % CI, 1.00-1.08; P = 0.013). The association was more stronger for per longer allele (OR = 1.07; 95 % CI, 1.01-1.12; P = 0.010). These results strongly suggest that there is a significant effect of AIB1 genetic variation on ovarian cancer risk, and AIB1 underlies the development of ovarian cancer.
authors.affiliation: Xiaoshan Hospital, Hangzhou, Zhejiang, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Han
authors.forename: Song
authors.initials: S
authors.lastname: Xie
authors.forename: Hongming
authors.initials: H
authors.lastname: Fang
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Yinquan
authors.initials: Y
authors.lastname: Han
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000328:Adult; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D020079:Terminal Repeat Sequences
chemical_list: D010455:Peptides; C097188:polyglutamine; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3