Genome-wide association studies have identified numerous genetic susceptibility loci for breast cancer, although these loci explain only a small proportion of heritability. Relatively few studies have assessed associations of breast cancer risk with copy number variation, another important source of genetic variation. As reported in Journal of the National Cancer Institute, a copy number variation genome-wide association study performed by Long and colleagues showed a strong association between a common deletion in APOBEC3 genes and increased breast cancer risk among Chinese women in Shanghai.
In stage 1 of the study, conducted in 2,623 patients breast with cancer and 1,946 controls, a common deletion in the APOBEC3 genes (P = 1.1 × 10−4) showed the strongest association with breast cancer risk among the 268 common copy number variations investigated (minor allele frequency ≥ 5%). In stage 2 of the study, in which the most promising copy number variation was replicated using real-time quantitative polymerase chain reaction (PCR) in another set of 4,254 patients and 4,387 controls, the deletion in APOBEC3 genes was associated with a 1.35 odds ratio for breast cancer (P = 9.6 × 10−22).
Analyses of all samples from both stages using quantitative PCR showed odds ratios of 1.31 (95% confidence interval = 1.21–1.42) for a one-copy deletion and 1.76 (95% confidence interval = 1.57–1.97) for a two-copy deletion (P = 2.0 × 10−24).
The authors concluded, “We provide convincing evidence for a novel breast cancer locus at the APOBEC3 genes. This [copy number variation] is one of the strongest common genetic risk variants identified so far for breast cancer.” ■
Long J, et al: J Natl Cancer Inst 105:573-579, 2013.