title: Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer.
abstract: The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165-7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25-6.64).
authors.affiliation: Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan. ksugano@tcc.pref.tochigi.jp
authors.forename: Kokichi
authors.initials: K
authors.lastname: Sugano
authors.forename: Seigo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Jiro
authors.initials: J
authors.lastname: Ando
authors.forename: Shin
authors.initials: S
authors.lastname: Takayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamata
authors.forename: Isao
authors.initials: I
authors.lastname: Sekiguchi
authors.forename: Megumi
authors.initials: M
authors.lastname: Ubukata
authors.forename: Tetsuro
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authors.lastname: Kodama
authors.forename: Masami
authors.initials: M
authors.lastname: Arai
authors.forename: Fujio
authors.initials: F
authors.lastname: Kasumi
authors.forename: Yasuo
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authors.lastname: Hirai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Jinno
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeda
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukutomi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Tsunematsu
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Masako
authors.initials: M
authors.lastname: Izumi
authors.forename: Shino
authors.initials: S
authors.lastname: Umezawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Komatsu
authors.forename: Naoko
authors.initials: N
authors.lastname: Arimori
authors.forename: Noriko
authors.initials: N
authors.lastname: Matoba
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Gondo
authors.forename: Shiro
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA