title: 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.
authors.affiliation: Department of Oncology & Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. ysuehiro@yamaguchi-u.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Takae
authors.initials: T
authors.lastname: Okada
authors.forename: Naoya
authors.initials: N
authors.lastname: Shikamoto
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zhan
authors.forename: Kohei
authors.initials: K
authors.lastname: Sakai
authors.forename: Naoko
authors.initials: N
authors.lastname: Okayama
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Nishioka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Furuya
authors.forename: Atsunori
authors.initials: A
authors.lastname: Oga
authors.forename: Shigeto
authors.initials: S
authors.lastname: Kawauchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Maeda
authors.forename: Michiko
authors.initials: M
authors.lastname: Tamesa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D016022:Case-Control Studies; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000097:blood / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005854:Germ Cells / Q000378:metabolism*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D004247:DNA