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

Xianan Bai,Shanshan Sun,Da Pang,Xianyu Zhang,Yongdong Jiang,Jingjing Xie

doi:10.18632/oncotarget.16359

Xianan Bai, Shanshan Sun + Show 4 more

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https://doi.org/10.18632/oncotarget.16359

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Abstract

BackgroundCytochrome 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.ResultsFirstly, 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 MethodsFour 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.ConclusionsCYP1A2 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.

Highlights

Breast cancer is the most common malignancy among women worldwide [1]
Firstly, single nucleotide polymorphisms (SNPs) rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated with age and menstruation status
SNP rs2470890 was correlated with CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P = 0.006, respectively)

Summary

Introduction

Breast cancer is the most common malignancy among women worldwide [1]. The crude mortality of breast cancer doubled from year 1973–1975 to year 2004–2005 in China [2]. A huge amount of studies reported the involvement of genetic polymorphisms in breast cancer susceptibility, studies of the genetic influence on disease progression and outcome are less frequent [3]. Some variations in the CYP3A4 gene have been observed to play significantly roles in the development and outcome of several types of cancer [20,21,22]. To date, lack of studies involving the effect of single nucleotide polymorphisms (SNPs) in the CYP1A2 and CYP3A4 genes on the prognosis and survival of patients with breast cancer. 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

Objectives

Methods

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