Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
Division of Genetics and Population Health, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, QLD, 4006, Australia.
Nat Commun. 2018 Oct 4;9(1):4083. 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.
在高外显率基因中发现的致病性变异可用于遗传性乳腺癌的诊断、治疗和监测。需要进行大规模研究，为日本未来的检测和变异分类过程提供信息。我们在 7051 名未经选择的乳腺癌患者和 11241 名日本裔女性对照中，对 11 个遗传性乳腺癌基因的编码区变异进行了病例对照关联研究。在此，我们鉴定出 244 种种系致病性变异。致病性变异在 5.7%的患者中发现，从 40 岁以下女性诊断的 15%到 80 岁以上患者的 3.2%不等，BRCA1/2 占所有年龄鉴定出的致病性变异的三分之二。BRCA1/2、PALB2 和 TP53 是重要的致病基因。BRCA1/2 或 PTEN 中存在致病性变异的患者诊断年龄明显较小。总之，BRCA1/2、PALB2 和 TP53 是日本女性不论诊断年龄大小的主要遗传性乳腺癌基因。
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