Jian Wenjing, Shao Kang, Qin Qi, Wang Xiaohong, Song Shufen, Wang Xianming
Department of Breast and Thyroid Surgery, Shenzhen Second people's Hospital, Shenzhen, 518035 China.
Department of Breast and Thyroid Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630 China.
Hered Cancer Clin Pract. 2017 Oct 30;15:19. doi: 10.1186/s13053-017-0079-4. eCollection 2017.
Breast cancer develops as a result of multiple gene mutations in combination with environmental risk factors. Causative variants in genes such as BRCA1 and/or BRCA2 have been shown to account for hereditary nature of certain breast cancers. However,other genes, such as ATM, PALB2, BRIP1, CHEK, BARD1, while lower in frequency, may also increase breast cancer risk. There are few studies examining the role of these causative variants. Our study aimed to examine the clinical and genetic characterization of hereditary breast cancer in a Chinese population.
We tested a panel of 27 genes implicated in breast cancer risk in 240 participants using Next-Generation Sequencing. The prevalence of genetic causative variants was determined and the association between causative variants and clinico-pathological characteristics was analyzed.
Causative variant rate was 19.2% in the breast cancer (case) group and 12.5% in the high-risk group. In the case group 2.5% of patients carried BRCA1 causative variant, 7.5% BRCA2 variants, 1.7% patients had MUTYH, CHEK or PALB2 variants, and 0.8% patients carried ATM, BARD1, NBN, RAD51C or TP53 variants. In the high-risk group 5.8% women carried MUTYH causative variants, 2.5% had causative variants in ATM, 1.7% patients had variants in BRCA2 and 0.8% in BARD1, BRIP1 or CDH1. There was no significant difference in the presence of causative variants among clinical stages of breast cancer, tumor size and lymph nodes status. However, eight of the 12 BRCA1/2 causative variants were found in the TNBC group.
We found increased genetic causative variants in the familial breast cancer group and in high-risk women with a family history of breast cancer. However, the variant MUTYH c.892-2A > G may not be directly associated with hereditary breast carcinoma.
乳腺癌是多种基因突变与环境风险因素共同作用的结果。已证实，BRCA1和/或BRCA2等基因中的致病变异可解释某些乳腺癌的遗传性。然而，其他基因，如ATM、PALB2、BRIP1、CHEK、BARD1，虽然频率较低，但也可能增加患乳腺癌的风险。很少有研究探讨这些致病变异的作用。我们的研究旨在探讨中国人群中遗传性乳腺癌的临床和基因特征。
我们使用下一代测序技术检测了240名参与者中一组与乳腺癌风险相关的27个基因。确定了基因致病变异的患病率，并分析了致病变异与临床病理特征之间的关联。
乳腺癌（病例）组的致病变异率为19.2%，高危组为12.5%。在病例组中，2.5%的患者携带BRCA1致病变异，7.5%携带BRCA2变异，1.7%的患者有MUTYH、CHEK或PALB2变异，0.8%的患者携带ATM、BARD1、NBN、RAD51C或TP53变异。在高危组中，5.8%的女性携带MUTYH致病变异，2.5%有ATM致病变异，1.7%的患者有BRCA2变异，0.8%有BARD1、BRIP1或CDH1变异。乳腺癌的临床分期、肿瘤大小和淋巴结状态之间致病变异的存在没有显著差异。然而，在三阴性乳腺癌组中发现了12个BRCA1/2致病变异中的8个。
我们发现家族性乳腺癌组和有乳腺癌家族史的高危女性中基因致病变异增加。然而，MUTYH基因c.892-2A>G变异可能与遗传性乳腺癌没有直接关联。
