title: Role of MMP-3 and MMP-9 and their haplotypes in risk of bladder cancer in North Indian cohort.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) play critical roles in cancer development and progression. Nonsynonymous single nucleotide polymorphisms (SNPs) in functional domain of MMP-3 and MMP-9 contribute appreciably to cancer predisposition and aggression. To test this proposition we examined whether six SNPs of the MMP-3 and MMP-9 genes are associated with risk of bladder cancer (BC) in a North Indian population.
  
  
  METHODS
  Six SNPs of MMP-3 and MMP-9 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a case-control study including 200 BC patients and 200 age/gender/ethnicity-matched controls.
  
  
  RESULTS
  Increased risk for BC susceptibility was observed in MMP-3 (1171) 5A/5A [P = 0.022; odds ratio (OR), 3.46; 95% confidence interval (CI), 1.20-9.98], MMP-9 (Q279R) QQ (P = 0.048; OR, 1.92; 95%CI, 1.01-3.66), MMP-9 (P574R) PR (P < 0.001; OR, 2.62; 95%CI, 1.71-4.03) and PR + RR (P < 0.001; OR, 2.59; 95%CI, 1.72-3.91) genotypes, and in R allele (P < 0.001; OR, 2.05; 95%CI, 1.47-2.85). Furthermore, significant association between MMP-9 Q279R, P574R polymorphism and smoking was observed in BC risk. Haplotype analysis too revealed significant association with 5A-A-G of MMP-3 haplotype (P = 0.022; OR, 1.99; 95%CI, 1.11-3.60) and with R-R (P = 0.001; OR, 2.00; 95%CI, 1.35-2.97) and Q-R (P < 0.001; OR, 2.97; 95%CI, 1.65-5.37) of MMP-9 haplotype. Genotype 5A/6A of MMP-3-1171 showed borderline risk and high recurrence-free survival in Bacillus Calmette-Guérin (BCG)-treated non-muscle-invasive BC (NMIBC) patients (log-rank P = 0.025).
  
  
  CONCLUSIONS
  Our data suggested that MMP-3-1171 5A/5A and MMP-9 (Q279R) QQ, MMP-9 (P574R) PR, PR + RR, and R allele are associated with high risk of BC.
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: Anil
authors.initials: A
authors.lastname: Mandhani
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
authors.forename: Rama D
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9