A single-nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances bladder cancer susceptibility

To explore the association between the promoter polymorphism (that influences the transcriptional level) of matrix metalloproteinase-1 (MMP-1, associated with tumour cell invasion and metastasis) and bladder cancer in a Turkish population. The MMP-1 polymorphism was assessed in 102 transitional cell carcinomas of the bladder (50 Ta, 52 T2-4) and in 94 age-, smoking- and gender-matched healthy volunteers. The polymerase chain reaction (PCR) assay was used to determine the MMP-1 genotypes. Genomic DNA used for the assay was extracted from peripheral blood lymphocytes. The frequency of the MMP-1 2G/2G genotype, which results in the highest MMP-1 transcriptional level, was compared to that of the 1G/1G plus 1G/2G genotypes. Of the 102 cases with bladder cancer, 49 (48%) showed the 2G/2G genotype, whereas it was found in 22 of the 94 controls (23%); this difference was statistically significant (P < 0.01; odds ratio 2.79, 95% confidence interval, CI, 1.53-5.60). However, there was no significant association between the 2G/2G genotype and tumour grade and pathological stage. We assessed the interaction between smoking status (former and current smokers, by their median pack years) and 2G/2G genotype; there was a significantly increased risk in heavy smokers (P < 0.001; odds ratio 3.21; 95% CI 1.33-5.60). These results suggest that the MMP-1 promoter polymorphism might be linked to susceptibility for bladder cancer.