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

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.