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Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Author information

1
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan. momozawa@riken.jp.
2
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
3
Division of Genetics and Population Health, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, 4006, Australia.
4
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
5
Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan.
6
FMC Tokyo Clinic, 1-3-2, Iidabashi, Chiyoda-ku, Tokyo, 102-0072, Japan.
7
Division of Genome Medicine, Institute for Genome Research, Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
8
Department of Genetic Medicine and Services, National Cancer Centre Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
9
Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
10
Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Centre Research Institute, 4-9-13 Yohnan, Tochigi, 320-0834, Japan.
11
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
12
Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
13
Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
14
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan. michiaki.kubo@riken.jp.

Abstract

Pathogenic variants in highly penetrant genes are useful for the diagnosis, therapy, and surveillance for hereditary breast cancer. Large-scale studies are needed to inform future testing and variant classification processes in Japanese. We performed a case-control association study for variants in coding regions of 11 hereditary breast cancer genes in 7051 unselected breast cancer patients and 11,241 female controls of Japanese ancestry. Here, we identify 244 germline pathogenic variants. Pathogenic variants are found in 5.7% of patients, ranging from 15% in women diagnosed <40 years to 3.2% in patients ≥80 years, with BRCA1/2, explaining two-thirds of pathogenic variants identified at all ages. BRCA1/2, PALB2, and TP53 are significant causative genes. Patients with pathogenic variants in BRCA1/2 or PTEN have significantly younger age at diagnosis. In conclusion, BRCA1/2, PALB2, and TP53 are the major hereditary breast cancer genes, irrespective of age at diagnosis, in Japanese women.

PMID:
30287823
PMCID:
PMC6172276
DOI:
10.1038/s41467-018-06581-8
[Indexed for MEDLINE]
Free PMC Article

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