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

• Published in: Nature communications Vol. 9; no. 1; pp. 4083 - 7
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-10-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 45/77; 631/208; 631/208/2489/1512; 631/208/514/2184; 631/208/727/2000; 631/67/1347; Adult; Aged; Aged, 80 and over; Asian People - genetics; BRCA1 protein; Breast cancer; Breast Neoplasms - genetics; Cancer; Case-Control Studies; Diagnosis; Female; Genes; Germ-Line Mutation; Health risk assessment; Heredity; Humanities and Social Sciences; Humans; Middle Aged; multidisciplinary; p53 Protein; Patients; PTEN protein; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06581-8

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.
Association between variants in 11 different genes and breast cancer risk has been established and sequencing of these genes is recommended to provide personalized diagnosis, therapy, and surveillance for the high-risk patients and their relatives. Here the authors analyse the frequency of germline pathogenic mutations in these genes specifically in a Japanese population.