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Identification and functional characterization of JWA polymorphisms and their association with risk of gastric cancer and esophageal squamous cell carcinoma in a Chinese population.

Authors
  • Tang, Wei-Yan
  • Wang, Lina
  • Li, Chunping
  • Hu, Zhi-Bin
  • Chen, Rui
  • Zhu, Yu-Jie
  • Shen, Hong-Bing
  • Wei, Qing-Yi
  • Zhou, Jian-Wei
Type
Published Article
Journal
Journal of toxicology and environmental health. Part A
Publication Date
Jun 01, 2007
Volume
70
Issue
11
Pages
885–894
Identifiers
PMID: 17479402
Source
Medline
License
Unknown

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.

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