Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.
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DOI：
10.1038/s41467-018-06581-8
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发表时间：
2018-10-04
影响因子：
16.6
通讯作者：
Kubo M
中科院分区：
文献类型：
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作者：
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
高外显基因的致病性变异对遗传性乳腺癌的诊断、治疗和监测有重要意义。需要进行大规模的研究，为今后的日语测试和变异分类过程提供信息。我们对7051名日本血统的乳腺癌患者和11,241名女性对照的11个遗传性乳腺癌基因编码区的变异进行了病例对照关联研究。在这里，我们确定了244个生殖系致病变异。在5.7%的患者中发现了致病性变异，范围从诊断为<40岁的女性的15%到≥80岁的患者的3.2%，BRCA 1/2解释了所有年龄段鉴定的致病性变异的三分之二。BRCA 1/2、PALB 2和TP 53是重要的致病基因。BRCA 1/2或PTEN致病性变异的患者在诊断时年龄显着年轻。总之，BRCA 1/2，PALB 2和TP 53是日本女性中主要的遗传性乳腺癌基因，与诊断时的年龄无关。11个不同基因的变异与乳腺癌风险之间的关联已经建立，建议对这些基因进行测序，为高危患者及其亲属提供个性化的诊断、治疗和监测。在这里，作者分析了这些基因中生殖系致病突变的频率，特别是在日本人群中。
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.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
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影响因子：
4.7
作者：
Nakamura K;Okada E;Ukawa S;Hirata M;Nagai A;Yamagata Z;Kiyohara Y;Muto K;Kamatani Y;Ninomiya T;Matsuda K;Kubo M;Nakamura Y;BioBank Japan Cooperative Hospital Group;Tamakoshi A
通讯作者：
Tamakoshi A
影响因子：
3.7
作者：
Colombo M;De Vecchi G;Caleca L;Foglia C;Ripamonti CB;Ficarazzi F;Barile M;Varesco L;Peissel B;Manoukian S;Radice P
通讯作者：
Radice P
影响因子：
4
作者：
Nakamura, Seigo;Takahashi, Masato;Shimizu, Tadao
通讯作者：
Shimizu, Tadao
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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