A Common Deletion in the APOBEC3 Genes and Breast Cancer Risk

• Published in: JNCI : Journal of the National Cancer Institute Vol. 105; no. 8; pp. 573 - 579
• Main Authors: Long, Jirong, Delahanty, Ryan J., Li, Guoliang, Gao, Yu-Tang, Lu, Wei, Cai, Qiuyin, Xiang, Yong-Bing, Li, Chun, Ji, Bu-Tian, Zheng, Ying, Ali, Simak, Shu, Xiao-Ou, Zheng, Wei
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 17.04.2013; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; APOBEC Deaminases; Asian People - genetics; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; China; Cytidine Deaminase; Cytosine Deaminase - genetics; DNA Copy Number Variations; Female; Gene Deletion; Genes; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Odds Ratio; Real-Time Polymerase Chain Reaction; Risk Assessment; Risk Factors; Tropical medicine; Tumors; Asia; China; Human; Breast disease; Breast cancer; Malignant tumor; Epidemiology; Mammary gland diseases; Cancerology; Gene; Risk factor; Deletion; Genetics; Public health; Cancer
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djt018

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. 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. 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)). 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.