Impact of MMP-3 and TIMP-3 gene polymorphisms on prostate cancer susceptibility in North Indian cohort.

Abstract

PURPOSE:

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.

MATERIALS AND 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.

CONCLUSION:

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: Priyanka Srivastava, Rakesh Kapoor, Rama Devi Mittal
• Journal: Gene (Gene) Vol. 530 Issue 2 Pg. 273-7 (Nov 10 2013) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 23872201 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Elsevier B.V. All rights reserved.

Chemical References

• TIMP3 protein, human
• Tissue Inhibitor of Metalloproteinase-3
• Matrix Metalloproteinase 3

Topics

• Aged
• Alleles
• Case-Control Studies
• Gene Frequency
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• India
• Male
• Matrix Metalloproteinase 3 (genetics)
• Middle Aged
• Neoplasm Grading
• Polymorphism, Genetic
• Prostatic Neoplasms (genetics)
• Risk
• Smoking
• Tissue Inhibitor of Metalloproteinase-3 (genetics)