title: The influence of functional polymorphisms in matrix metalloproteinase 9 on survival of breast cancer patients in a Chinese population.
abstract: 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.
authors.affiliation: Department of General Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Fangmeng
authors.initials: F
authors.lastname: Fu
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Chen
authors.forename: Meng
authors.initials: M
authors.lastname: Huang
authors.forename: He-Guang
authors.initials: HG
authors.lastname: Huang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D001943:Breast Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000401:mortality*; D002277:Carcinoma / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000401:mortality*; D002681:China / Q000453:epidemiology; D005260:Female; D060045:Genes, Modifier / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011153:Population; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9