Functional polymorphisms in the promoter regions of MMP2 and MMP3 are not associated with melanoma progression Journal Article


Authors: Cotignola, J.; Roy, P.; Patel, A.; Ishill, N.; Shah, S.; Houghton, A.; Coit, D.; Halpern, A.; Busam, K.; Berwick, M.; Orlow, I.
Article Title: Functional polymorphisms in the promoter regions of MMP2 and MMP3 are not associated with melanoma progression
Abstract: Background. The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression. Methods. We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test. Results. All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729. Conclusion. This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression. © 2007 Cotignola et al; licensee BioMed Central Ltd.
Keywords: survival; adolescent; adult; child; preschool child; aged; aged, 80 and over; child, preschool; middle aged; unclassified drug; gene sequence; human cell; major clinical study; promoter region; genetics; disease course; cancer growth; cancer risk; cancer patient; polymerase chain reaction; phenotype; melanoma; metastasis; nevus; genotype; enzymology; pathology; heterozygote; germ line; correlation coefficient; disease progression; multivariate analysis; kaplan meier method; chi square test; logistic regression analysis; polymorphism, genetic; fisher exact test; race; genetic polymorphism; sample; sex; gelatinase a; stromelysin; log rank test; lentigo; matrix metalloproteinase 2; promoter regions (genetics); melting point; mmp2 protein, human; mmp3 protein, human; matrix metalloproteinase 3
Journal Title: Journal of Negative Results in BioMedicine
Volume: 6
ISSN: 1477-5751
Publisher: Biomed Central Ltd  
Date Published: 2007-10-24
Start Page: 9
Language: English
DOI: 10.1186/1477-5751-6-9
PUBMED: 17958893
PROVIDER: scopus
PMCID: PMC2148054
DOI/URL:
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 17 November 2011" - "Source: Scopus"
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MSK Authors
  1. Allan C Halpern
    303 Halpern
  2. Irene Orlow
    192 Orlow
  3. Daniel Coit
    422 Coit
  4. Klaus J Busam
    540 Busam
  5. Alan N Houghton
    273 Houghton
  6. Nicole Marie Leoce
    86 Leoce
  7. Pampa Roy
    32 Roy
  8. Ami Patel
    24 Patel
  9. Shivang S Shah
    4 Shah