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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。
Objective To investigate the mutation frequency of single nucleotide polymorphism (SNP) in the coding region of breast cancer susceptibility gene (BRCA) 1/2 in patients with genetic high risk breast cancer in China and to explore the relationship between the polymorphism of the corresponding locus and clinicopathological features Relationship. Methods The DNA of peripheral blood mononuclear cells from 69 patients with genetic high risk breast cancer was collected. The 49 exon sequences of BRCA1 / 2 coding region were detected by the second generation sequencing. At the same time, clinical pathological data of all patients were collected, including age of onset, age of menarche, first gestational age, tumor TNM stage, immunohistochemical characteristics, whether breast cancer and family history, analyzed the BRCA1 / 2 coding region Relationship between the polymorphisms and clinicopathological features of tumor. Results A total of 34 SNP loci were found, of which 14 were located in BRCA1 and 20 were located in BRCA2. There were 18 high frequency loci and 16 low frequency loci. There was a correlation between rs80356892 polymorphism in BRCA1 coding region and the clinicopathological features of the tumor. The mutations in the BRCA1 locus tended to have bilateral breast cancer (P = 0.005), family history (P = 0.029) and triple negative breast cancer P <0.001). The mutation of rs80356892 was negatively correlated with the expression of estrogen receptor and progesterone receptor. Conclusion SNP in BRCA1 / 2 coding region is associated with the risk of breast cancer and the clinicopathological features of breast cancer. Therefore, the detection of SNP will be helpful for the assessment of risk and the screening and prevention of hereditary breast cancer.