Germline Copy Number Variations Associated with Breast Cancer Susceptibility.pdf

RESEARCH ARTICLE Germline copy number variations associated with breast cancer susceptibility in a Japanese population Yutaka Suehiro Takae Okada Naoya Shikamoto Yibo Zhan Kohei Sakai Naoko Okayama Mitsuaki Nishioka Tomoko Furuya Atsunori Oga Shigeto Kawauchi Noriko Maeda Michiko Tamesa Yukiko Nagashima Shigeru Yamamoto Masaaki Oka Yuji Hinoda Kohsuke Sasaki Received: 7 September 2012 /Accepted: 11 December 2012 /Published online: 30 December 2012 # The Author(s) 2012. This article is published with open access at S Abstract Although copy number variations (CNVs) are expected to affect various diseases, little is known about the association between CNVs and breast cancer suscepti- bility. Therefore, we investigated this relation. Array com- parative genomic hybridization was performed to search for candidate CNVs related to breast cancer susceptibility. Sub- sequent 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 Hcn on 1p36.12 (P0.0001), 2.9 and 2.2 for Hcn on 3q26.1 (P0.0001), 1.2 and 1.8 for Hcn on 15q26.3 (P0.0001), 1.0 and 1.5 for Hcn on 15q26.3 (P0.0001), and 1.1 and 1.7 for Hcn on 15q26.3 (P0.0001), respectively. Interestingly, nine or more copies of Hcn 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 predic- tion of breast cancer susceptibility. These find