title: Association of promoter polymorphisms in MMP2 and TIMP2 with prostate cancer susceptibility in North India.
abstract: OBJECTIVE
  The importance of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in tumor progression is well documented. MMP2/TIMP2 system has a significant impact on the development and progression of cancer and genetic polymorphisms in the promoters of MMP2 (-1306C/T, 735C/T) and TIMP2 (-418G/A, -303C/T) are correlated with decreased enzyme activity. We sought to determine whether genetic polymorphisms in MMP2 and TIMP2 polymorphisms may be associated with varying risk of prostate cancer (PCa) in men in North India.
  
  
  METHODS
  Genotyping was done by PCR-restriction fragment length polymorphism method in 190 histologically confirmed PCa patients and 200 unrelated, healthy, age-matched individuals of similar ethnicity.
  
  
  RESULTS
  Patients with MMP2 (-1306) CT genotype as well as T allele were at higher risk of PCa (p = 0.018; OR = 1.68 and p = 0.015; OR = 1.52). This effect was even more evident in the case of the T allele carrier (CT + TT) (p = 0.011; OR = 1.71). MMP2 (735) C>T, TIMP2 (-418) G>C and TIMP2 (-303) C>T polymorphism demonstrated no association. However, TIMP2 (-418) GC was found to be involved in progression of PCa but not in initiation. Haplotype results demonstrated that MMP2 (1306T-735C) and TIMP2 (418G-303T) were associated with a 1.5- and 1.8-fold increased risk, respectively.
  
  
  CONCLUSIONS
  Our data indicated that MMP2-1306C>T gene polymorphism contributes to PCa susceptibility. These findings suggested MMP2 variants as a predictor of PCa progression risk among North Indian men. We assume that analysis of these gene polymorphisms can help identify patient subgroups at high risk of poor disease outcome.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Srivastava
authors.forename: Tasleem A
authors.initials: TA
authors.lastname: Lone
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000328:Adult; D000368:Aged; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
chemical_list: C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2