Affiliations: Department of Urology and Renal Transplantation,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Note: [] Corresponding author: Dr. Rama Devi Mittal, Department of
Urology, SGPGIMS, Raebareli Road, Lucknow-226014, India. Tel.: +91 522 2668004
8, Ext. 2116; Fax: +91 522 2668 017; E-mail: ramamittal@gmail.com; rmittal@sgpgi.ac.in
Abstract: Matrix metalloproteinases (MMPs) contribute to tumor invasion and
microenvironment, hence are associated with bladder cancer risk. We therefore,
tested whether polymorphisms in MMP genes modify the risk of bladder cancer
(BC) and whether smoke exposure modifies this risk. Genotyping was performed in
200 BC patients and 200 controls by polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP). MMP1-1607 2G/2G and
MMP7-181 GG genotype were associated with increased risk of BC
(p < 0.001; OR, 3.04; 95% CI- 1.71–5.39 and p, 0.005; OR,
2.38; 95% CI- 1.30–4.34) respectively. Smokers in BC patients showed
significant increased risk for the same SNPs (p, 0.006; OR, 3.20; 95% CI-
1.40–7.31 and p, 0.009; OR, 2.85; 95% CI- 1.30–6.23 respectively).
Haplotype analysis too revealed significant association with G/2G of
MMP1-519-1607 (p< 0.001; OR, 2.62; 95% CI- 1.68–4.09).
The 2G allele carrier (1G/2G + 2G/2G) of MMP1-1607 showed a protective
effect and high recurrence free survival in Bacillus Calmette-Guérin
(BCG) treated non muscle invasive BC (NMIBC) patients (log rank p, 0.030). Our
data suggested that MMP1-1607 2G and MMP7-181 G allele were
associated with high risk of BC, which was quite evident amongst smokers too.
BCG treated NMIBC patients reflected protective effect for 2G allele carrier
(1G/2G + 2G/2G) of MMP1-1607. This study provided new
support for the association of MMP1-1607 and MMP7-181 in bladder cancer
development, the tumorigenic effect of which was observed to be more enhanced
in case of tobacco exposure.
