Objective: This case-control study was aimed to detect the single nucleotide polymorphisms (SNPs) in JWA promoter region, to assess the effect of SNP on transcriptional activity, and to probe the relationship between SNP and the risk of bladder cancer.
Methods: The design of one control per case was adopted. The JWA gene promoter region in 155 patients with bladder cancer and in 155 cancer-free controls was amplified by PCR-SSCP technique, and the SNP were confirmed by direct DNA sequencing. The recombinant plasmids of JWA promoter fragment which contain the SNP were constructed as CAT reporter gene and were transfected transiently into NIH 3T3 cells for disclosing whether SNP changes the transcriptional activity of the promoter.
Results: A novel SNP -76 G-->C at promoter region of JWA gene was found. The frequencies of the C allele and GC genotype at JWA promoter -76G-->C in bladder cancer group (10.00% and 20.00% respectively) were significantly higher than those in control group (5.16% and 10.32% respectively) (P < 0.05). The transcriptional activity of -76GC allele genotype was significantly down-regulated as compared with that of -76GG allele genotype (P < 0.01). Multivariate logistic regression analysis revealed that JWA polymorphism at promoter -76G-->C is an independent novel risk factor for bladder cancer.
Conclusion: The JWA -76G-->C variant genotype may play an important role in transcription regulation of JWA gene and in the susceptibility to bladder cancer.