title: 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 (-76GC) 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 -76GC polymorphism, another novel SNP (454CA in exon2 and 723TG in exon 3) of JWA was identified. The -76GC 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, -76GC, 454CA, and 723TG, appear to contribute to the etiology of bladder cancer.
authors.affiliation: Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Li
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Zhu
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Qi-Zhan
authors.initials: QZ
authors.lastname: Liu
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
authors.forename: Zheng-Dong
authors.initials: ZD
authors.lastname: Zhang
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Zhou
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004587:Electrophoresis, Agar Gel; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013781:Texas / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: C484566:ARL6IP5 protein, human; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins