Absence of a correlation between the presence of a single nucleotide polymorphism in the matrix metalloproteinase 1 promoter and outcome in patients of chondrosarcoma.
OBJECTIVE
Increased levels of matrix metalloproteinase 1 (MMP-1) expression have been associated with poor outcome in chondrosarcoma. The existence of a single nucleotide polymorphism creating an Ets-binding site in the MMP-1 promoter may be one mechanism for elevated MMP-1 transcription. The aim of our study was to identify the prevalence of this single nucleotide polymorphism (SNP) in chondrosarcoma patients, to determine its correlation with disease outcome, and to discern whether it could serve as a prognostic marker in patients with chondrosarcoma.


METHODS
Sixty-seven chondrosarcoma specimens were selected sequentially from an established tumor bank with a median duration of 47 months follow-up (range, 24 to 179 months). DNA was extracted, amplified with PCR, and sequenced to determine presence (GG) or absence of the Ets-binding site created by the SNP.


RESULTS
Eighteen (27%) samples were homozygous for the absence of the Ets site, 34 (51%) were heterozygous for the SNP, and 15 (22%) were homozygous for the SNP. The 5-year overall survival rate for patients was 78, 80, and 84%, respectively (P = 0.5527). The disease-free survival rate was 16, 63, and 76%, respectively (P = 0.0801). The 5-year disease-free survival rate for patients with the homozygous G/G genotype was 16%, compared with 71% for patients who were either homozygous or heterozygous for the GG allele (P = 0.0444).


CONCLUSIONS
Despite a statistical correlation between MMP-1 gene expression and outcome in chondrosarcoma, this study demonstrates an absence of a correlation between the presence of the SNP and prognosis in patients with chondrosarcoma.
Fong
Yi-Chin
YC
Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
Dutton
Charyl M
CM
Cha
Stephen S
SS
Garamszegi
Nandor
N
Sim
Franklin H
FH
Scully
Sean P
SP
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D001665:Binding Sites; D014408:Biomarkers, Tumor; D002813:Chondrosarcoma / Q000235:genetics* / Q000473:pathology*; D004247:DNA / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D013997:Time Factors; D014158:Transcription, Genetic; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004247:DNA; D020781:Matrix Metalloproteinase 1