Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer.
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).
Sugano
Kokichi
K
Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan. ksugano@tcc.pref.tochigi.jp
Nakamura
Seigo
S
Ando
Jiro
J
Takayama
Shin
S
Kamata
Hiroyuki
H
Sekiguchi
Isao
I
Ubukata
Megumi
M
Kodama
Tetsuro
T
Arai
Masami
M
Kasumi
Fujio
F
Hirai
Yasuo
Y
Ikeda
Tadashi
T
Jinno
Hiromitsu
H
Kitajima
Masaki
M
Aoki
Daisuke
D
Hirasawa
Akira
A
Takeda
Yuko
Y
Yazaki
Kumiko
K
Fukutomi
Takashi
T
Kinoshita
Takayuki
T
Tsunematsu
Ryuichiro
R
Yoshida
Teruhiko
T
Izumi
Masako
M
Umezawa
Shino
S
Yagata
Hiroshi
H
Komatsu
Hiroko
H
Arimori
Naoko
N
Matoba
Noriko
N
Gondo
Nobuhisa
N
Yokoyama
Shiro
S
Miki
Yoshio
Y
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