title: A common deletion in the APOBEC3 genes and breast cancer risk.
abstract: BACKGROUND
  Genome-wide association studies (GWASs) have identified multiple genetic susceptibility loci for breast cancer. However, these loci explain only a small fraction of the heritability. Very few studies have evaluated copy number variation (CNV), another important source of human genetic variation, in relation to breast cancer risk.
  
  
  METHODS
  We conducted a CNV GWAS in 2623 breast cancer patients and 1946 control subjects using data from Affymetrix SNP Array 6.0 (stage 1). We then replicated the most promising CNV using real-time quantitative polymerase chain reaction (qPCR) in an independent set of 4254 case patients and 4387 control subjects (stage 2). All subjects were recruited from population-based studies conducted among Chinese women in Shanghai.
  
  
  RESULTS
  Of the 268 common CNVs (minor allele frequency ≥ 5%) investigated in stage 1, the strongest association was found for a common deletion in the APOBEC3 genes (P = 1.1×10(-4)) and was replicated in stage 2 (odds ratio =1.35, 95% confidence interval [CI] = 1.27 to 1.44; P = 9.6×10(-22)). Analyses of all samples from both stages using qPCR data produced odds ratios of 1.31 (95% CI = 1.21 to 1.42) for a one-copy deletion and 1.76 (95% CI = 1.57 to 1.97) for a two-copy deletion (P = 2.0×10(-24)).
  
  
  CONCLUSIONS
  We provide convincing evidence for a novel breast cancer locus at the APOBEC3 genes. This CNV is one of the strongest common genetic risk variants identified so far for breast cancer.
authors: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203-1738, USA. jirong.long@vanderbilt.edu
authors: Jirong
authors: J
authors: Long
authors: Ryan J
authors: RJ
authors: Delahanty
authors: Guoliang
authors: G
authors: Li
authors: Yu-Tang
authors: YT
authors: Gao
authors: Wei
authors: W
authors: Lu
authors: Qiuyin
authors: Q
authors: Cai
authors: Yong-Bing
authors: YB
authors: Xiang
authors: Chun
authors: C
authors: Li
authors: Bu-Tian
authors: BT
authors: Ji
authors: Ying
authors: Y
authors: Zheng
authors: Simak
authors: S
authors: Ali
authors: Xiao-Ou
authors: XO
authors: Shu
authors: Wei
authors: W
authors: Zheng
mesh_terms: D000071478:APOBEC Deaminases; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002681:China; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase