Bai Xianan, Xie Jingjing, Sun Shanshan, Zhang Xianyu, Jiang Yongdong, Pang Da
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin150040, China.
Oncotarget. 2017 Jun 13;8(24):38367-38377. doi: 10.18632/oncotarget.16359.
Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the differentiation of clinical outcomes among breast cancer women. This study aimed to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4 genes with clinicopathological features, protein expression and prognosis of breast cancer in the northern Chinese population.
Firstly, SNP rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated with age and menstruation status. And SNP rs11636419 and rs17861162 were associated with the P53 status. Secondly, SNP rs2470890 was correlated with CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P = 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan-Meier 5 year survival curves showed that patients carrying genotypes CT or TT had a worse OS compared with the genotype CC carriers under both codominant and dominant model (P < 0.001, P < 0.001, respectively).
Four single nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer patients using the SNaPshot method. The associations of four polymorphisms with protein expression and clinicopathological characteristics were evaluated by Pearson's chi-square test. The Cox hazard regression analysis and Kaplan-Meier survival analysis were performed to evaluate the relationship between the SNPs and overall survival (OS) of breast cancer.
CYP1A2 rs2470890 was significantly associated with the prognosis of patients with breast cancer and could serve as an independent impact factor of prognosis of breast carcinoma.
细胞色素P450(CYP)1A2和CYP3A4可能在乳腺癌女性临床结局的分化中起作用。本研究旨在分析中国北方人群中CYP1A2和CYP3A4基因的遗传多态性与乳腺癌临床病理特征、蛋白表达及预后的相关性。
首先,CYP1A2基因中的单核苷酸多态性(SNP)rs11636419、rs17861162和rs2470890与年龄和月经状态显著相关。并且SNP rs11636419和rs17861162与P53状态相关。其次,在共显性和显性模型下,SNP rs2470890与CYP1A2蛋白表达相关(分别为P = 0.017,P = 0.006)。第三,对于SNP rs2470890,Kaplan-Meier 5年生存曲线显示,在共显性和显性模型下,携带CT或TT基因型的患者与CC基因型携带者相比总生存期更差(分别为P < 0.001,P < 0.001)。
采用SNaPshot方法对459例乳腺癌患者成功进行了4个单核苷酸多态性的基因分型。通过Pearson卡方检验评估4种多态性与蛋白表达及临床病理特征的相关性。进行Cox风险回归分析和Kaplan-Meier生存分析以评估SNP与乳腺癌总生存期(OS)之间的关系。
CYP1A2 rs2470890与乳腺癌患者的预后显著相关,可作为乳腺癌预后的独立影响因素。