Role of MMP-3 and MMP-9 and their haplotypes in risk of bladder cancer in North Indian cohort.

Abstract

PURPOSE:

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).

CONCLUSION:

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: Priyanka Srivastava, Anil Mandhani, Rakesh Kapoor, Rama D Mittal
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 17 Issue 11 Pg. 3068-75 (Nov 2010) ISSN: 1534-4681 [Electronic] United States
• PMID: 20574775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Matrix Metalloproteinase 3
• Matrix Metalloproteinase 9

Topics

• Aged
• Carcinoma, Transitional Cell (genetics)
• Case-Control Studies
• Cohort Studies
• Female
• Genotype
• Haplotypes
• Humans
• India
• Male
• Matrix Metalloproteinase 3 (genetics)
• Matrix Metalloproteinase 9 (genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Urinary Bladder Neoplasms (genetics)