title: Identification and functional characterization of JWA polymorphisms and their association with risk of gastric cancer and esophageal squamous cell carcinoma in a Chinese population.
abstract: Recently, a novel single nucleotide polymorphism (SNP) in the promoter of the JWA gene (-76G --> C) was identified that may alter the transcription activity and thus play a role in increased risk of bladder cancer. In this study, a screen for more novel variants in the JWA exons was undertaken by using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by a PCR-restriction fragment length polymorphism (PCR-RFLP) method and evaluating the functions of newl identified JWA -76G --> C using the reporter gene assay. In addition to the -76G --> C polymorphism, another novel SNP (723T --> G) in exon 3 of JWA was identified. In a case-control study of these two SNPs in 413 gastric cancer and 250 esophageal squamous-cell carcinoma (ESCC) patients and 814 cancer-free controls in a Chinese population, data showed that both SNPs were associated with enhanced risk of these cancers. The reporter gene assay showed that the -76C variant allele lost its response to benzo[a]pyrene (BaP) exposure, compared to the -76G allele. In addition, the JWA -76C allele was found to be associated with increased gastric and esophageal cancer risks in this study population. Further studies are needed to substantiate the biological significance and related mechanisms underlying the associations.
authors.affiliation: Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, China.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Tang
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Chunping
authors.initials: C
authors.lastname: Li
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Hu
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Zhu
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shen
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Zhou
mesh_terms: D044466:Asian People / Q000235:genetics*; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D016172:DNA Fingerprinting; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D017930:Genes, Reporter / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors; D013274:Stomach 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; D001564:Benzo(a)pyrene