| 摘要: |
| 目的 研究中国遗传高风险乳腺癌患者乳腺癌易感基因（BRCA）1/2编码区单核苷酸多态性（SNP）的突变频率，并探讨其相应位点多态性与肿瘤临床病理特征的关系。方法 收集提取69例遗传高风险乳腺癌患者的外周血单个核细胞DNA，运用二代测序技术对BRCA1/2编码区的49个外显子序列进行检测分析。同时收集所有患者的临床病理资料，包括发病年龄、初潮年龄、首次妊娠年龄、肿瘤的TNM分期、免疫组化特征、是否为双侧乳腺癌及是否具有家族史等，分析BRCA1/2编码区相应位点多态性与肿瘤临床病理特征的相关性。结果 研究共发现34个SNP位点，其中14个位于BRCA1，20个位于BRCA2；有高频位点18个及低频位点16个。BRCA1编码区rs80356892位点多态性与肿瘤临床病理特征存在相关性，该位点突变的患者倾向于双侧乳腺癌（P=0.005）、存在家族史（P=0.029）以及三阴性乳腺癌（P<0.001），且rs80356892位点突变与雌激素受体、孕激素受体表达呈负相关。结论 BRCA1/2编码区SNP与乳腺癌发病风险及乳腺癌临床病理特征相关，因此SNP的检测将有助于发病风险的评估及遗传性乳腺癌的筛查、防治。 |
| 关键词: 疾病遗传易感性 乳腺肿瘤 BRCA基因 单核苷酸多态性 突变频率 病理特征 |
| DOI：10.16781/j.0258-879x.2017.03.0276 |
| 投稿时间：2016-11-26修订日期：2017-02-18 |
| 基金项目:国家自然科学基金（8150111616）. |
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| Mutation frequency of SNP in BRCA1/2 coding region and its relationship with clinicopathological features of Chinese patients with hereditarily high-risk breast cancer |
| FANG Min,ZHANG Xiao-xi,YU Yue,LI Heng-yu,WU Kai-nan,LIN Jian,SHENG Yuan* |
(Department of Breast and Thyroid Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Objective To explore the mutation frequency of single nucleotide polymorphism (SNP) in the breast cancer susceptibility gene (BRCA)1/2 coding region and its relationship with clinicopathological features of Chinese patients with hereditarily high-risk breast cancer. Methods We extracted the DNA of peripheral blood mononuclear cells from 69 Chinese hereditarily high-risk patients with breast cancer, and detected the sequences of 49 exons in BRCA1/2 coding region by second-generation sequencing technology. At the same time, we collected the clinicopathological data of all patients, including the age at diagnosis, the age at menarche, first pregnancy age, TNM stage, immunohistochemical status, whether it was bilateral breast cancer and/or with family history, and analyzed the relationship of site polymorphism of BRCA1/2 coding region with clinicopathological features of breast cancer. Results A total of 34 SNPs were identified, among which 14 were located in the BRCA1 and 20 in the BRCA2 coding region, including 18 high frequency sites and 16 low frequency sites. The rs80356892 site polymorphism of BRCA1 coding region was significantly correlated with the clinicopathological features of breast cancer. The patients with rs80356892 site mutation were inclined to have bilateral breast cancer (P=0.005), family history (P=0.029) and triple negative breast cancer (P<0.001). In addition, SNP in rs80356892 site was negatively correlated with the expressions of estrogen receptor and progesterone receptor. Conclusion SNP in BRCA1/2 coding region are associated with the onset risk and the clinicopathological features of breast cancer. The detection of SNP may contribute to risk assessment of breast cancer and screening and prevention of hereditary breast cancer. |
| Key words: genetic predisposition to disease breast neoplasms BRCA genes single nucleotide polymorphism mutation frequency pathological features |
