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Gene. 2013 Nov 10;530(2):273-7. doi: 10.1016/j.gene.2013.06.087. Epub 2013 Jul 17.

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

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1
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow-226014, Uttar Pradesh, India.

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.

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

PMID:
23872201
DOI:
10.1016/j.gene.2013.06.087
[Indexed for MEDLINE]
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