title: Genetic polymorphisms in AURKA, BRCA1, CCNE1 and CDK2 are associated with ovarian cancer susceptibility among Chinese Han women.
abstract: BACKGROUND
  Centrosome aberrations and cell-cycle deregulation have important implications for ovarian cancer development. The AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation.
  
  
  METHODS
  Using a haplotype-based analysis, this study aimed to investigate whether genetic polymorphisms in these four genes may contribute to ovarian cancer susceptibility. A total of 22 single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 287 cases of ovarian serous cystadenocarcinomas and 618 age-matched cancer-free controls from the Chinese Han population, and then haplotype blocks were reconstructed according to our genotyping data and linkage disequilibrium (LD) status of these SNPs.
  
  
  RESULTS
  For AURKA, we found that haplotype GA [rs6064391 (T→G)+rs911162 (G→A)] was strongly associated with decreased ovarian cancer risk (adjusted OR=0.31, 95% CI=0.15-0.63, P=0.0012). For BRCA1, we found that haplotype CGTAG was associated with decreased ovarian cancer risk (adjusted OR=0.64, 95% CI=0.41-0.98, P=0.0417). Moreover, women harboring homozygous GA/CGTAG haplotypes showed the lowest risk (OR=0.12, 95% CI=0.02-0.94, P=0.0438). In CCNE1, the SNPs rs3218035 and rs3218042 were significantly associated with increased ovarian cancer risk (rs3218035: adjusted OR=5.20, 95% CI=1.85-14.52, P=0.0017; rs3218042: adjusted OR=4.98, 95% CI=1.75-14.19, P=0.0027). For CDK2, no significant association was found.
  
  
  CONCLUSIONS
  This study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may affect ovarian cancer susceptibility in Chinese Han women.
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Zheng
authors.forename: Aiping
authors.initials: A
authors.lastname: Song
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ruan
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: Dongge
authors.initials: D
authors.lastname: Liu
authors.forename: Xianghong
authors.initials: X
authors.lastname: Li
authors.forename: Hongyan
authors.initials: H
authors.lastname: Guo
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xinxia
authors.initials: X
authors.lastname: Tian
authors.forename: Weigang
authors.initials: W
authors.lastname: Fang
mesh_terms: D044466:Asian People / Q000235:genetics*; D064096:Aurora Kinase A / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D019927:Cyclin E / Q000235:genetics*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D060148:HapMap Project; D006801:Humans; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: AURKA; BRCA1; CCNE1; CDK2; Ovarian cancer; Single nucleotide polymorphism (SNP)