Functional Polymorphisms of JWA Gene are Associated with Risk of Bladder Cancer

Abstract

The JWA gene is a novel cell differentiation-related gene thought to be a responsive gene in response to DNA damage and repair induced by environmental stressors. Recently, a novel single nucleotide polymorphism (SNP) was identified in the promoter of the JWA gene (−76G→C) that may alter the transcription activity and thus play a role in increased risk of bladder cancer. Further, studies were conducted to screen for more novel variants in the JWA exons by using PCR-SSCP (polymerase chain reaction–single-strand conformation polymorphism) followed by PCR-RFLP (PCR restriction fragment length polymorphism) methods. Finally, the functional relevance of the newly identified genetic variants in a hospital-based case-control study of 215 bladder cancer patients and 250 cancer-free controls was evaluated. In addition to the −76G→C polymorphism, another novel SNP (454C→A in exon2 and 723T→G in exon 3) of JWA was identified. The −76G→C allele and genotype frequencies were found to vary in different ethnic groups. The −76C allele and 454A allele were both associated with significantly increased risk of bladder cancer. In contrast, the 723GG genotype was associated with a decreased risk of bladder cancer. Furthermore, −76C and 454A together increased the risk of bladder caner using haplotype and stratification analysis. In conclusion, the three novel functional genetic polymorphisms of JWA gene, −76G→C, 454C→A, and 723T→G, appear to contribute to the etiology of bladder cancer.