Genetic polymorphisms of matrix metalloproteinases: susceptibility and prognostic implications for prostate cancer.
OBJECTIVE
Prostate cancer is the most common tumor in males in Brazil. Single nucleotide polymorphisms have been demonstrated to exist in the promoter regions of matrix metalloproteinase genes and they are associated with the development and progression of some cancers. We investigated the correlation between MMP1, 2, 7 and 9 polymorphisms with susceptibility to prostate cancer, and classic prognostic parameters of prostate cancer.


METHODS
Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction using TaqMan(R) fluorescent probes.


RESULTS
For the MMP1 gene the polymorphic allele was more common in the control group than in the prostate cancer group (p <0.001). For the MMP9 gene the incidence of the polymorphic homozygote genotype was higher in the prostate cancer group (p <0.001). For higher stage tumors (pT3) a polymorphic allele in the MMP2 gene was more common (p = 0.026). When considering Gleason score, the polymorphic homozygote genotype of MMP9 was more common in Gleason 6 or less tumors (p = 0.003), while a polymorphic allele in the MMP2 gene was more common in Gleason 7 or greater tumors (p = 0.042).


CONCLUSIONS
MMP1 and MMP2 may protect against prostate cancer development and MMP9 may be related to higher risk. In contrast, MMP9 polymorphism was associated with a lower Gleason score and MMP2 polymorphism was associated with nonorgan confined disease.
Dos Reis
Sabrina Thalita
ST
Urology Department, Laboratory of Medical Investigation, Faculdade de Medicina da Universidade de São Paulo, Brazil.
Pontes
José
J
Villanova
Fabiola Elizabeth
FE
Borra
Priscila Maria de Andrade
PM
Antunes
Alberto Azoubel
AA
Dall'oglio
Marcos Francisco
MF
Srougi
Miguel
M
Leite
Katia Ramos Moreira
KR
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D004273:DNA, Neoplasm / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1