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

Yukihide Momozawa; Yusuke Iwasaki; Michael T. Parsons; Yoichiro Kamatani; Atsushi Takahashi; Chieko Tamura; Toyomasa Katagiri; Teruhiko Yoshida; Seigo Nakamura; Kokichi Sugano; Yoshio Miki; Makoto Hirata; Koichi Matsuda; Amanda B. Spurdle; Michiaki Kubo

doi:10.1038/s41467-018-06581-8

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

Yukihide Momozawa, Yusuke Iwasaki, Michael T. Parsons, Yoichiro Kamatani, Atsushi Takahashi, Chieko Tamura, Toyomasa Katagiri, Teruhiko Yoshida, Seigo Nakamura, Kokichi Sugano, Yoshio Miki, Makoto Hirata, Koichi Matsuda, Amanda B. Spurdle, Michiaki Kubo

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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.

Original language	English
Article number	4083
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06581-8
Publication status	Published - 01-12-2018

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Momozawa, Y., Iwasaki, Y., Parsons, M. T., Kamatani, Y., Takahashi, A., Tamura, C., Katagiri, T., Yoshida, T., Nakamura, S., Sugano, K., Miki, Y., Hirata, M., Matsuda, K., Spurdle, A. B., & Kubo, M. (2018). Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nature communications, 9(1), [4083]. https://doi.org/10.1038/s41467-018-06581-8

Momozawa, Yukihide ; Iwasaki, Yusuke ; Parsons, Michael T. ; Kamatani, Yoichiro ; Takahashi, Atsushi ; Tamura, Chieko ; Katagiri, Toyomasa ; Yoshida, Teruhiko ; Nakamura, Seigo ; Sugano, Kokichi ; Miki, Yoshio ; Hirata, Makoto ; Matsuda, Koichi ; Spurdle, Amanda B. ; Kubo, Michiaki. / Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. In: Nature communications. 2018 ; Vol. 9, No. 1.

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

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.",

author = "Yukihide Momozawa and Yusuke Iwasaki and Parsons, {Michael T.} and Yoichiro Kamatani and Atsushi Takahashi and Chieko Tamura and Toyomasa Katagiri and Teruhiko Yoshida and Seigo Nakamura and Kokichi Sugano and Yoshio Miki and Makoto Hirata and Koichi Matsuda and Spurdle, {Amanda B.} and Michiaki Kubo",

note = "Funding Information: We thank the people who participated in this study. We acknowledge C. Inai, N. Hakozaki, H. Hashinokuchi, and other staffs of the Laboratory for Genotyping Development, RIKEN Center for the Integrative Medical Sciences, and the staff of the BioBank Japan project. This work was conducted as part of the BioBank Japan Project supported by the Japan Agency for Medical Research and Development and by the Ministry of Education, Culture, Sports, Sciences, and Technology of the Japanese government. A.B. Spurdle is supported by an Australian NHMRC Senior Research Fellowship.",

year = "2018",

month = dec,

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doi = "10.1038/s41467-018-06581-8",

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Momozawa, Y, Iwasaki, Y, Parsons, MT, Kamatani, Y, Takahashi, A, Tamura, C, Katagiri, T, Yoshida, T, Nakamura, S, Sugano, K, Miki, Y, Hirata, M, Matsuda, K, Spurdle, AB & Kubo, M 2018, 'Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls', Nature communications, vol. 9, no. 1, 4083. https://doi.org/10.1038/s41467-018-06581-8

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. / Momozawa, Yukihide; Iwasaki, Yusuke; Parsons, Michael T.; Kamatani, Yoichiro; Takahashi, Atsushi; Tamura, Chieko; Katagiri, Toyomasa; Yoshida, Teruhiko; Nakamura, Seigo; Sugano, Kokichi; Miki, Yoshio; Hirata, Makoto; Matsuda, Koichi; Spurdle, Amanda B.; Kubo, Michiaki.

In: Nature communications, Vol. 9, No. 1, 4083, 01.12.2018.

Research output: Contribution to journal › Article › peer-review

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T1 - Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls

AU - Momozawa, Yukihide

AU - Iwasaki, Yusuke

AU - Parsons, Michael T.

AU - Kamatani, Yoichiro

AU - Takahashi, Atsushi

AU - Tamura, Chieko

AU - Katagiri, Toyomasa

AU - Yoshida, Teruhiko

AU - Nakamura, Seigo

AU - Sugano, Kokichi

AU - Miki, Yoshio

AU - Hirata, Makoto

AU - Matsuda, Koichi

AU - Spurdle, Amanda B.

AU - Kubo, Michiaki

N1 - Funding Information: We thank the people who participated in this study. We acknowledge C. Inai, N. Hakozaki, H. Hashinokuchi, and other staffs of the Laboratory for Genotyping Development, RIKEN Center for the Integrative Medical Sciences, and the staff of the BioBank Japan project. This work was conducted as part of the BioBank Japan Project supported by the Japan Agency for Medical Research and Development and by the Ministry of Education, Culture, Sports, Sciences, and Technology of the Japanese government. A.B. Spurdle is supported by an Australian NHMRC Senior Research Fellowship.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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

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