A common deletion in the APOBEC3 genes and breast cancer risk.

Long J, Delahanty RJ, Li G, Gao YT, Lu W, Cai Q, Xiang YB, Li C, Ji BT, Zheng Y, Ali S, Shu XO, Zheng W
J Natl Cancer Inst. 2013 105 (8): 573-9

PMID: 23411593 · PMCID: PMC3627644 · DOI:10.1093/jnci/djt018

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.

MeSH Terms (17)

Adult Aged Asian Continental Ancestry Group Breast Neoplasms China Cytosine Deaminase DNA Copy Number Variations Female Gene Deletion Genetic Predisposition to Disease Genome-Wide Association Study Humans Middle Aged Odds Ratio Real-Time Polymerase Chain Reaction Risk Assessment Risk Factors

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