The associations of genetic polymorphisms in CYP1A2 and CYP3A4 with clinical outcomes of breast cancer patients in northern China

2017 
// Xianan Bai 1 , Jingjing Xie 1 , Shanshan Sun 1 , Xianyu Zhang 1 , Yongdong Jiang 1 , Da Pang 1 1 Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin150040, China Correspondence to: Da Pang, email: pangda@ems.hrbmu.edu.cn Yongdong Jiang, email: jiangyongdonghmu@126.com Keywords: SNP, CYP1A2, CYP3A4, breast cancer, prognosis indicator Received: December 06, 2015      Accepted: February 27, 2017      Published: March 18, 2017 ABSTRACT Background: 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. Results: 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). Materials and Methods: 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. Conclusions: 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.
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