The Influence of Functional Polymorphisms in Matrix Metalloproteinase 9 on Survival of Breast Cancer Patients in a Chinese Population

被引:13
|
作者
Fu, Fangmeng [1 ]
Wang, Chuan [1 ]
Chen, Li-Min [2 ]
Huang, Meng [3 ]
Huang, He-Guang [1 ]
机构
[1] Fujian Med Univ, Affiliated Union Hosp, Dept Gen Surg, Fuzhou 350001, Peoples R China
[2] Fujian Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Fuzhou 350001, Peoples R China
[3] Fujian Ctr Dis Control & Prevent, Fuzhou, Peoples R China
关键词
GENE POLYMORPHISMS; EXPRESSION; MMP-9; RISK; ASSOCIATION; COLLAGENASE; METASTASIS; CARCINOMA; BINDING;
D O I
10.1089/dna.2012.1928
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Matrix metalloproteinase 9 (MMP9) plays a critical role in cancer aggression, and its overexpression is associated with a poor prognosis in breast cancer. Because common genetic variants can alter the expression or function of MMPs, we hypothesized that potentially functional single-nucleotide polymorphisms (SNPs) in the MMP9 gene may be associated with the survival of patients with invasive breast cancer. In this case-cohort follow-up study, a total of 245 breast cancer patients in southeast China were investigated, and five haplotype tagging SNPs (htSNPs) in the MMP9 gene were genotyped by using matrix-assisted laser desorption/ionization mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism methods. Disease-free survival (DFS) and distance disease-free survival (DDFS) analyses were used to identify the SNPs associated with prognosis and determine their interdependence with the recognized prognostic factors. We found that the MMP9 rs3787268 GA + AA genotypes were significantly associated with poor DFS and DDFS of patients with breast cancer (log-rank p-values 0.045 and 0.028, respectively), especially in some subgroups of patients. Multivariate Cox regression and stepwise COX regression analyses suggested that rs3787268 may be a candidate independent biomarker to predict breast cancer survival in this population. Further, among estrogen receptor (ER) + /epidermal growth receptor 2 (HER-2) - patients, the rs3787268 GA + AA genotypes and rs17577 GG genotype showed a locus-dosage effect between combined the genotypes and decreased survival (adjusted HR 2.59, 95% confidence interval [CI] 1.29-5.19 and adjusted HR 3.25, 95% CI 1.39-7.58, respectively, for DFS and DDFS). Our results suggest that the polymorphisms in the MMP9 gene may be genetic modifiers for breast cancer prognosis in this Chinese population.
引用
收藏
页码:274 / 282
页数:9
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