Genetic polymorphisms in the MMP-2 and MMP-9 genes and breast cancer phenotype.
The matrix metalloproteinases (MMPs) have been shown to play important roles in cancer progression. In this study we examined whether common genetic variants in two key MMPs are associated with phenotypic features of breast cancers and patient outcome. A single nucleotide polymorphism in the promoter region of MMP-2 (-1306 C-->T) abolishes Sp1 binding and is associated with lower transcriptional activity, while another in the promoter region of MMP-9 (-1562 C-->T) increases the transcription of this gene. MMP-2 TT homozygous patients had smaller tumors (p=0.006) and contained lower concentrations of estrogen receptor (ER; p=0.002) compared to patients with the MMP-2 CC or CT genotype. Homozygosity for the MMP-2 -1306 T allele was associated with markedly different patient survival depending upon tumor ER status. For patients with ER negative tumors, the MMP-2 TT genotype was associated with poor survival (2/8 patients alive at end of study, 25%) compared to the CC or CT genotypes (59/70, 84%; p < 0.001). For patients with ER positive tumors, the MMP-2 TT genotype was associated with a trend for very good survival (10/10, 100%) compared to the CC or CT genotypes (130/157, 83%; p=0.16). The MMP-9 -1562 T allele was associated with features of good prognosis including non-ductal type histology, positive ER status and the absence of TP53 mutation. Patients with MMP-9 -1562 CT or TT genotypes showed marginally better prognosis compared to CC homozygotes (p=0.06). These findings suggest that breast cancer phenotype and outcome can be influenced by common functional polymorphisms in MMP genes.
Grieu
Fabienne
F
Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands.
Li
Wei Qi
WQ
Iacopetta
Barry
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000235:genetics*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010641:Phenotype; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016019:Survival Analysis
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9