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 andMMP7-181 GG genotype were associated with increased risk of BC (p<0.001; OR, 3.04; 95% CI1.71–5.39 and p, 0.005; OR, 2.38; 95% CI1.30–4.34) respectively. Smokers in BC patients showed significant increased risk for the same SNPs (p, 0.006; OR, 3.20; 95% CI1.40–7.31 and p, 0.009; OR, 2.85; 95% CI1.30–6.23 respectively). Haplotype analysis too revealed significant association with G/2G ofMMP1-519-1607 (p< 0.001; OR, 2.62; 95% CI1.68–4.09). The 2G allele carrier (1G/2G + 2G/2G) ofMMP1-1607 showed a protective effect and high recurrence free survival in Bacillus Calmette-Guerin (BCG) treated non muscle invasive BC (NMIBC) patients (log rank p, 0.030). Our datasuggested that MMP11607 2G and MMP7181 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) ofMMP1-1607. 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.
Highlights
Transitional cell carcinoma (TCC) accounts for 90% of all cases of bladder cancer (BC) and remains as a significant cause of morbidity and death [1]
Clinical research showed the presence of Matrix metalloproteinases (MMPs)-1 in cancer cells, and that MMP1 expression is associated with a poor prognosis [21]
In the present study we have focused on two promoter polymorphism of MMP1
Summary
Transitional cell carcinoma (TCC) accounts for 90% of all cases of bladder cancer (BC) and remains as a significant cause of morbidity and death [1]. Most BC (70–80%) present as non-muscle-invasive papillary tumors which recur frequently (50–80%), but progress less often (5–30%) to invade bladder muscle wall. The remaining 20–30% of BC is aggressive muscle-invasive tumors that have a much higher risk of metastasis, despite radical treatment [2]. Over the last three decades, intravesical immunotherapy with the biological response modifier Bacillus Calmette-Guerin (BCG) has been established as the most effective adjuvant treatment for preventing local recurrences and tumor progression following transurethral resection of non-muscle invasive BC [3], the response rate for BCG treatment is only 60% to 70%. P. Srivastava et al / Bladder cancer risk associated with genotypic polymorphism established a major role for BCG immunotherapy in urological oncology
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