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 | |
| Publication status | Published - 01-12-2018 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
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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
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 -