title: Impact of MMP-3 and TIMP-3 gene polymorphisms on prostate cancer susceptibility in North Indian cohort.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) have been implicated in progression and metastases of different tumors. The balance between the MMPs and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMP) seem to be an important factor related to its role. The purpose of this study was to evaluate polymorphisms in the MMP-3 and TIMP-3 genes for their associations with prostate cancer (PCa) risk in North Indians.
  
  
  METHODS
  Genotypes were determined by PCR-RFLP (Polymerase Chain Reaction Restriction Fragment Length Polymorphism) method in 150 PCa patients and 200 age matched controls of similar ethnicity.
  
  
  RESULTS
  We found significant association in the MMP-3(1171)5A/6A and TIMP-3 (1298) C/T polymorphism with PCa risk. Variant genotype (5A/5A) of MMP-3(1171)5A/6A polymorphism had a high PCa risk (p=0.037, OR=3.52, 95%CI=1.08-11.5). Individuals with TIMP-3 (1298) CT genotype as well as T allele showed reduced risk of PCa (p<0.001; OR=0.31; 95%CI=0.18-0.52, and p=0.001; OR=0.49; 95%CI=0.32-0.75). This effect was even more evident in case of T allele carrier (CT+TT) (p<0.001; OR=0.36; 95%CI=0.22-0.59). Overall no significant association was observed statistically in MMP-3 and TIMP-3 with any of the grading stages and smoking habits in PCa. Haplotype analysis of MMP-3 showed that A-5A-A was associated with three folds (OR=3.06; 95%CI=1.71-5.47; p<0.001) increased risk in PCa patients.
  
  
  CONCLUSIONS
  This is the first reported association between polymorphisms in the MMP-3 and TIMP-3 gene and PCa risk and supports the hypothesis that the protease/antiprotease balance has an important role. Due to the small sample size further investigations need to be done to prove a statistical significant correlation between the MMP/TIMP expression and clinicopathological parameters.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow-226014, Uttar Pradesh, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Srivastava
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk; D012907:Smoking; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*
chemical_list: C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D019278:Matrix Metalloproteinase 3
keywords: DRE; Digital rectal examination; Haplotype; MMP; Matrix metalloproteinase; Matrix metalloproteinases; PCR-RFLP; PCa; PSA; Polymerase chain reaction–restriction fragment length polymorphism; Polymorphism; Prostate cancer; Prostate specific antigen; SNP; Single-nucleotide polymorphisms; TIMP; Tissue Inhibitors of metalloproteinases; Tissue inhibitors of metalloproteinase