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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish
Article number4083
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 01-12-2018

Fingerprint

oncogenes
Neoplasm Genes
breast
Genes
Breast Neoplasms
genes
cancer
penetrants
surveillance
Case-Control Studies
therapy
coding
Testing

All Science Journal Classification (ASJC) codes

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

Cite this

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.
@article{9303af3a0df24fb4aaefbe170cbc0bb7,
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",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41467-018-06581-8",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

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 journalArticle

TY - JOUR

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85054450193&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054450193&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-06581-8

DO - 10.1038/s41467-018-06581-8

M3 - Article

C2 - 30287823

AN - SCOPUS:85054450193

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4083

ER -