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3 years ago 癌症易感基因知多少 by 生信技能树
最近有一些小伙伴看到了我六年前的《直播我的基因组》系列，觉得我可能是基因检测解读方面的“专家”，哈哈哈！
我目前的研究其实主要是集中于癌症病人的后天性的突变，并不是先天性的突变。虽然说有大约15%的癌症病人是先天性基因缺陷导致的，但我自己并没有往那方面进行知识整理。如果咱们《生信技能树》的读者群有表达能力还不错的，也看完了我六年前的《直播我的基因组》系列，愿意把其中一些技术每次口语化，写一写科普小短文，可以留言撩我哈，恭候大驾哦！
风险基因3个等级
综述：Acta Oncologica Volume 58, 2019 - Issue 2 链接：https://www.tandfonline.com/doi/full/10.1080/0284186X.2018.1529428 把乳腺癌易感基因的风险分成了3个等级；
High-risk variants: Very rare in the population with a minor allele frequency of <0.005. The conferred relative risk of breast cancer is higher than 4. Moderate-risk variants: Rare, with a minor allele frequency of 0.005–0.01. Pathogenic variants confer a relative risk of 2–4. Low-risk variants: Minor allele frequency >0.05 and conferred risk of breast cancer of less than 1.5-fold
乳腺癌的30个易感基因
于April 2020发表在《The Journal of Molecular Diagnostics》杂志的文章是：《Germline Mutation in 1338 BRCA-Negative Chinese Hereditary Breast and/or Ovarian Cancer Patients: Clinical Testing with a Multigene Test Panel》，链接在：https://www.sciencedirect.com/science/article/abs/pii/S1525157820300362
High-risk breast cancer patients who were negative for BRCA1, BRCA2, TP53 and PTEN were selected from the Hong Kong Hereditary Breast Cancer Family Registry between 2007-2016.
In the study, 745 patients were subjected to 30-gene panel by next-generation sequencing (Color Genomics).
乳腺癌的13个易感基因
文献是：Ann Oncol. 2015 ， 总结了那些乳腺癌相关的胚系遗传性的致病突变，共11个基因，结论很简单：
Up to 25% of hereditary cases are due to a mutation in one of the few identified rare, but highly penetrant genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11), which confer up to an 80% lifetime risk of breast cancer. An additional 2%-3% of cases are due to a mutation in a rare, moderate-penetrance gene (e.g. CHEK2, BRIP1, ATM, and PALB2), each associated with a twofold increase in risk. 最后是低风险的多态性位点，A small number of low-penetrance alleles have been identified using advanced genetic testing methods.
乳腺癌的12个易感基因
在 February 4, 2021 发表于NEJM杂志的文章：《Population-Based Study of Genes Implicated in Breast Cancer》，
链接是：https://www.nejm.org/do/10.1056/NEJMdo005961/full/ 主要是结论是：
The prevalence of pathogenic variants in the 12 established genes among women with breast cancer (N=32,247) was 5.03%, and the prevalence in unaffected women (N=32,544) was 1.63%.
对来自25个国家高达11万3000位女性的基因样本进行大范围的基因检测，确定了12个基因 的突变和乳腺癌发病风险的升高存在直接的联系：ATM、BRCA1、BRCA2、CHEK2、PALB2、BARD1、RAD51C、RAD51D、PTEN、NF1、MSH6和TP53基因。
乳腺癌的11个易感基因
2018年NC的一篇日本人群队列文章：Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls 只关心了11个基因，
该研究纳入了7093 female breast cancer patients 和 11,260 female controls，有意思的是他们居然纳入了男性，We also examined 53 male breast cancer patients and 12,520 male controls using the same criteria.
受研究课题影响太大了
可以看到，某个基因是否被判定为癌症易感基因，取决于地理位置，研究单位纳入的病人数量，以及研究设计之初的基因数量。
https://mp.weixin.qq.com/s/w-05bDmdyFC8j7DX6FOwkg