title: Matrix Metalloproteinase-9 (MMP-9) polymorphisms in patients with cutaneous malignant melanoma.
abstract: BACKGROUND
  Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs) play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk.
  
  
  METHODS
  We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis.
  
  
  RESULTS
  We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site.
  
  
  CONCLUSIONS
  This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA. cotignoj@mskcc.org
authors.forename: Javier
authors.initials: J
authors.lastname: Cotignola
authors.forename: Boris
authors.initials: B
authors.lastname: Reva
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
authors.forename: Nicole
authors.initials: N
authors.lastname: Ishill
authors.forename: Shaokun
authors.initials: S
authors.lastname: Chuai
authors.forename: Ami
authors.initials: A
authors.lastname: Patel
authors.forename: Shivang
authors.initials: S
authors.lastname: Shah
authors.forename: Gretchen
authors.initials: G
authors.lastname: Vanderbeek
authors.forename: Daniel
authors.initials: D
authors.lastname: Coit
authors.forename: Klaus
authors.initials: K
authors.lastname: Busam
authors.forename: Allan
authors.initials: A
authors.lastname: Halpern
authors.forename: Alan
authors.initials: A
authors.lastname: Houghton
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008545:Melanoma / Q000201:enzymology / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: D020780:Matrix Metalloproteinase 9