- 作者：Priyanka Srivastava ; Tasleem A. Lone ; Rakesh Kapoor ; Rama Devi Mittal ; ramamittal@gmail.com
- 关键词：Haplotype ; Matrix metalloproteinases ; PCR-RFLP ; Prostate cancer ; Polymorphism ; Tissue inhibitors of metalloproteinases
- 刊名：Archives of Medical Research
- 出版年：2012
- 期刊代码：24_01884409
- 类别：med
- 出版时间：February, 2012
- 卷：43
- 期：2
- 页码：117-124
- 文件大小：237 K
Background and Aims
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 (鈭?em>1306C/T, 735C/T) and TIMP2 (鈭?em>418G/A, 鈭?em>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聽= 0.018; OR聽= 1.68 and p聽= 0.015; OR聽= 1.52). This effect was even more evident in the case of the T allele carrier (CT聽+ TT) (p聽= 0.011; OR聽= 1.71). MMP2 (735) C>T, TIMP2 (鈭?em>418) G>C and TIMP2 (鈭?03) C>T polymorphism demonstrated no association. However, TIMP2 (鈭?em>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.