Germline copy number variations associated with breast cancer susceptibility in a Japanese population

Abstract

Although copy number variations (CNVs) are expected to affect various diseases, little is known about the association between CNVs and breast cancer susceptibility. Therefore, we investigated this relation. Array comparative genomic hybridization was performed to search for candidate CNVs related to breast cancer susceptibility. Subsequent quantitative real-time polymerase chain reaction was carried out for confirmation. We found seven CNV markers associated with breast cancer risk. The means of the relative copy numbers of patients with a history of breast cancer and women in the control group were 0.8 and 1.8 for Hs06535529-cn on 1p36.12 (P < 0.0001), 2.9 and 2.2 for Hs03103056-cn on 3q26.1 (P < 0.0001), 1.2 and 1.8 for Hs03899300-cn on 15q26.3 (P < 0.0001), 1.0 and 1.5 for Hs03908783-cn on 15q26.3 (P < 0.0001), and 1.1 and 1.7 for Hs03898338-cn on 15q26.3 (P < 0.0001), respectively. Interestingly, nine or more copies of Hs04093415-cn on 22q12.3 were found only in 8/193 (4.1 %) patients with a history of breast cancer and in none of the controls (P = 0.0081). Similarly, 12 or more copies of Hs040908898-cn on 22q12.3 were found only in 7/193 (3.6 %) patients with a history of breast cancer and in none of the controls (P = 0.016). A combination of two CNVs resulted in 80.3 % sensitivity, 80.6 % specificity, 82.4 % positive predictive value, and 78.3 % negative predictive value for the prediction of breast cancer susceptibility. These findings may lead to a new means of risk assessment for breast cancer. Confirmatory studies using independent data sets are needed to support our findings. © 2012 The Author(s).