Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer

Kokichi Sugano, Seigo Nakamura, Jiro Ando, Shin Takayama, Hiroyuki Kamata, Isao Sekiguchi, Megumi Ubukata, Tetsuro Kodama, Masami Arai, Fujio Kasumi, Yasuo Hirai, Tadashi Ikeda, Hiromitsu Jinno, Masaki Kitajima, Daisuke Aoki, Akira Hirasawa, Yuko Takeda, Kumiko Yazaki, Takashi Fukutomi, Takayuki KinoshitaRyuichiro Tsunematsu, Teruhiko Yoshida, Masako Izumi, Shino Umezawa, Hiroshi Yagata, Hiroko Komatsu, Naoko Arimori, Noriko Matoba, Nobuhisa Gondo, Shiro Yokoyama, Yoshio Miki

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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).

Original languageEnglish
Pages (from-to)1967-1976
Number of pages10
JournalCancer science
Volume99
Issue number10
DOIs
Publication statusPublished - 2008 Nov 3

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sugano, K., Nakamura, S., Ando, J., Takayama, S., Kamata, H., Sekiguchi, I., Ubukata, M., Kodama, T., Arai, M., Kasumi, F., Hirai, Y., Ikeda, T., Jinno, H., Kitajima, M., Aoki, D., Hirasawa, A., Takeda, Y., Yazaki, K., Fukutomi, T., ... Miki, Y. (2008). Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. Cancer science, 99(10), 1967-1976. https://doi.org/10.1111/j.1349-7006.2008.00944.x