中国大样本乳腺癌患者癌症易感基因突变研究正式发表

11-16 04:23 首页 SIBCS


  携带癌症易感基因种系突变的乳腺癌患者,与无突变患者相比,临床意义及治疗方案选择可能不同。目前,癌症易感基因检测多局限于家族性和早发性乳腺癌患者,相关研究样本量小、缺乏对突变患者临床意义及其预后的分析。因此,对中国大样本连续非选择性乳腺癌患者进行多个癌症易感基因突变及其相关临床意义的研究极为迫切。


  2017年10月15日,美国癌症研究学会《临床癌症研究》正式发表北京大学肿瘤医院孙洁、孟桦、姚璐、欧阳涛、李金锋、王天峰、范照青、范铁、林本耀、解云涛和贝瑞基因的研究报告,对中国大样本连续非选择性乳腺癌患者BRCA等癌症易感基因种系突变的现患率及其临床意义进行了调查。


  该研究于2003年10月~2015年5月从北京大学肿瘤医院乳腺癌预防治疗中心连续入组中国乳腺癌患者8085例,不对年龄或家族史进行限制,其中91.7%为I~III期原发可手术乳腺癌,使用62基因组对46个癌症易感基因种系突变进行检测。


  结果发现,9.2%的患者携带致病突变。其中,5.3%的患者携带BRCA突变(BRCA1为1.8%,BRCA2为3.5%),2.9%携带其他乳腺癌易感基因,1.0%携带其他癌症易感基因。


  各个分子亚型的BRCA和其他乳腺癌易感基因突变现患率:

  • 最高:三阴性乳腺癌,分别为11.2%和3.8%

  • 最低:HR阴性HER2阳性乳腺癌,分别为 1.8%和1.6%


  经过中位随访50个月(范围1~152个月)


  BRCA1突变携带者与非携带者相比:

  • 无病生存显著较差(未校正风险比:1.60,95%置信区间:1.10~2.34,P=0.014)

  • 疾病特异生存较差(未校正风险比:1.96,95%置信区间:1.03~3.65,P=0.040)


  BRCA2突变携带者与非携带者相比,无病生存和疾病特异生存相似。


  因此,对于该大样本连续非选择性人群,9.2%的乳腺癌患者携带癌症易感基因致病突变。对于四个分子亚型,三阴性乳腺癌的乳腺癌易感基因突变现患率最高,HR阴性HER2阳性乳腺癌的乳腺癌易感基因突变现患率最低。


相关阅读


Clin Cancer Res. 2017 Oct 15;23(20):6113-6119.


Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients.


Sun J, Meng H, Yao L, Lv M, Bai J, Zhang J, Wang L, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Xie Y.


Peking University Cancer Hospital & Institute, Beijing, P. R. China; Berry Genomics, Beijing, P. R. China.


PURPOSE: The prevalence of mutations in cancer susceptibility genes such as BRCA1 and BRCA2 and other cancer susceptibility genes and their clinical relevance are largely unknown among a large series of unselected breast cancer patients in the Chinese population.


EXPERIMENTAL DESIGN: A total of 8,085 consecutive unselected Chinese breast cancer patients were enrolled. Germline mutations in 46 cancer susceptibility genes were detected using a 62-gene panel.


RESULTS: Pathogenic mutations were identified in 9.2% of patients among the 8,085 unselected breast cancer patients. Of these, 5.3% of patients carried a BRCA1 or BRCA2 mutation (1.8% in BRCA1 and 3.5% in BRCA2), 2.9% carried other breast cancer susceptibility genes (BOCG) and 1.0% carried another cancer susceptibility genes. Triple-negative breast cancers had the highest prevalence of BRCA1/2 mutations (11.2%) and other BOCG mutations (3.8%) among the four molecular subgroups, whereas ER-/PR-HER2+ breast cancers had the lowest mutations in BRCA1/2 (1.8%) and BOCG (1.6%). In addition, BRCA1 mutation carriers had a significant worse disease-free survival [unadjusted hazard ratio (HR) 1.60; 95% confidence interval (CI) 1.10-2.34; P = 0.014] and disease-specific survival (unadjusted HR 1.96; 95% CI, 1.03-3.65; P = 0.040) than did non-carriers, whereas no significant difference in survival was found between BRCA2 mutation carriers and non-carriers.


CONCLUSIONS: 9.2% of breast cancer patients carry a pathogenic mutation in cancer susceptibility genes in this large unselected series. Triple-negative breast cancers have the highest prevalence of mutations in BRCA1 /2 and other breast cancer susceptibility genes among the four molecular subgroups, whereas ER-/PR-HER2+ breast cancers had the lowest mutations in these genes.


PMID: 28724667


DOI: 10.1158/1078-0432.CCR-16-3227










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