Li Wen-Feng, Hu Zhen, Rao Nan-Yan, Song Chuang-Gui, Zhang Bin, Cao Ming-Zhi, Su Feng-Xi, Wang Yong-Sheng, He Ping-Qing, Di Gen-Hong, Shen Kun-Wei, Wu Jiong, Lu Jin-Song, Luo Jian-Min, Liu Xiao-Yi, Zhou Jie, Wang Lei, Zhao Lin, Liu Yan-Bing, Yuan Wen-Tao, Yang Lin, Shen Zhen-Zhou, Huang Wei, Shao Zhi-Ming
Department of Oncology, Breast Cancer Institute, Cancer Hospital/Cancer Institute, Institutes of Biomedical Science, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, PR China.
Breast Cancer Res Treat. 2008 Jul;110(1):99-109. doi: 10.1007/s10549-007-9708-3. Epub 2007 Sep 13.
To have an overview of the role of BRCA1 and BRCA2 genes among Chinese high-risk breast cancer patients, we analyzed 489 such high-risk breast cancer patients from four breast disease clinical centers in China, by using PCR-DHPLC or SSCP-DNA sequencing analysis. Allelotype analysis was done at five short tandem repeat (STR) markers in or adjacent to BRCA1 on the recurrent mutation carriers. For those analyzed both genes, 8.7% of early-onset breast cancer cases and 12.9% of familial breast cancer cases had a BRCA1 or BRCA2 mutation, as compared with the 26.1% of cases with both early-onset breast cancer and affected relatives. For those reporting malignancy family history other than breast/ovarian cancer, the prevalence of BRCA1/2 mutation is about 20.5%, and it was significantly higher than the patients only with family history of breast/ovarian cancer (P = 0.02). The family history of ovarian cancer (26.7% vs. 11.9%) and stomach cancer (23.8% vs. 11.8%) doubled the incidence of BRCA1/2, but the difference did not reach the statistical significance. Two recurrent mutations in BRCA1, 1100delAT and 5589del8, were identified. The recurrent mutations account for 34.8% BRCA1 mutations in our series. Similar allelotypes were detected in most STR status for those harboring the same mutations. The BRCA1 associated tumors were more likely to exhibit a high tumor grade, negative C-erbB-2/neu status and triple negative (ER, PgR and C-erbB-2/neu negative) status (P < 0.05). We recommended the BRCA1 and BRCA2 genetic analysis could be done for high-risk breast cancer patient in Chinese population, especially for those with both early-onset breast cancer and affected relatives. There may be some degree of shared ancestry for the two recurrent BRCA1 mutations in Chinese.
为了全面了解BRCA1和BRCA2基因在中国高危乳腺癌患者中的作用，我们运用聚合酶链反应-变性高效液相色谱法（PCR-DHPLC）或单链构象多态性- DNA测序分析法，对来自中国四个乳腺疾病临床中心的489例高危乳腺癌患者进行了分析。对复发突变携带者中BRCA1内部或其附近的五个短串联重复序列（STR）标记进行了等位基因分型分析。在那些对两个基因均进行分析的患者中，早发性乳腺癌病例的8.7%以及家族性乳腺癌病例的12.9%存在BRCA1或BRCA2突变，相比之下，早发性乳腺癌且有患病亲属的病例中这一比例为26.1%。对于那些报告有除乳腺癌/卵巢癌之外的恶性肿瘤家族史的患者，BRCA1/2突变的患病率约为20.5%，显著高于仅有乳腺癌/卵巢癌家族史的患者（P = 0.02）。卵巢癌家族史（26.7%对11.9%）和胃癌家族史（23.8%对11.8%）使BRCA1/2的发病率翻倍，但差异未达到统计学意义。在BRCA1中鉴定出两个复发突变，即1100delAT和5589del8。这些复发突变在我们的研究系列中占BRCA1突变的34.8%。在大多数STR状态下，对于携带相同突变的个体检测到了相似的等位基因类型。与BRCA1相关的肿瘤更有可能表现出高肿瘤分级、C-erbB-2/neu阴性状态以及三阴性（雌激素受体、孕激素受体和C-erbB-2/neu均为阴性）状态（P < 0.05）。我们建议对中国人群中的高危乳腺癌患者进行BRCA1和BRCA2基因分析，尤其是对于那些早发性乳腺癌且有患病亲属的患者。在中国，这两个BRCA1复发突变可能存在一定程度的共同祖先。
