Open AccessCross‐sectional analysis of germline BRCA 1 and BRCA 2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer
Author(s) -
Sugano Kokichi,
Nakamura Seigo,
Ando Jiro,
Takayama Shin,
Kamata Hiroyuki,
Sekiguchi Isao,
Ubukata Megumi,
Kodama Tetsuro,
Arai Masami,
Kasumi Fujio,
Hirai Yasuo,
Ikeda Tadashi,
Jinno Hiromitsu,
Kitajima Masaki,
Aoki Daisuke,
Hirasawa Akira,
Takeda Yuko,
Yazaki Kumiko,
Fukutomi Takashi,
Kinoshita Takayuki,
Tsunematsu Ryuichiro,
Yoshida Teruhiko,
Izumi Masako,
Umezawa Shino,
Yagata Hiroshi,
Komatsu Hiroko,
Arimori Naoko,
Matoba Noriko,
Gondo Nobuhisa,
Yokoyama Shiro,
Miki Yoshio
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00944.x
Subject(s) - breast cancer , family history , ovarian cancer , medicine , odds ratio , proband , confidence interval , oncology , brca mutation , germline mutation , cancer , genetic counseling , genetic testing , male breast cancer , gynecology , mutation , genetics , biology , gene
The prevalence of BRCA 1/2 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 BRCA 1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA 1 mutations in 17 subjects (12.6%) and 15 types of BRCA 2 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 BRCA 1/2 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). ( Cancer Sci 2008; 99: 1967–1976)