Short rare MUC6 minisatellites-5 alleles influence susceptibility to gastric carcinoma by regulating gene expression

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Title
Short rare MUC6 minisatellites-5 alleles influence susceptibility to gastric carcinoma by regulating gene expression
Author(s)
J A Kwon; Sang-Yeop Lee; E K Ahn; S Y Seol; M C Kim; S J Kim; S I Kim; In-Sun Chu; S H Leem
Bibliographic Citation
Human Mutation, vol. 31, no. 8, pp. 942-949
Publication Year
2010
Abstract
The human MUC6 gene, which is reported to be expressed in the stomach and gall bladder, is clustered on chromosome 11p15.5 with other secreted mucins. In this study, the genomic structure of MUC6 has been analyzed and five VNTR (minisatellites; MS1-MS5) were identified. These minisatellites were analyzed in genomic DNA extracted from 1,103 controls, 470 gastric cancer patients, and multigenerational families. Five novel minisatellites were found to be polymorphic and transmitted through meiosis by Mendelian inheritance in families. We evaluated allelic variation in these minisatellites to determine if such variation affected the susceptibility to gastric cancer. A significant association (odds ratio [OR]=7.08) between short rare MUC6-MS5 alleles and relative risks were observed for gastric cancer (95% confidence interval [CI], 1.43-35.19; P=0.005). To investigate the function of minisatellite alleles of MUC6-MS5, we examined the effects on gene expression from luciferase reporters when inserted with minisatellites. Interestingly, when the shortest allele (7TR) was inserted in the promoter, the expression level decreased over 20-fold (P<0.001) in normal and cancer cell lines. Furthermore, the cancerspecific rare allele (TR8) also showed decreased expression levels in cancer cells. Therefore, we suggest that the short rare MUC6-MS5 alleles may be related to cancer development by the regulation of MUC6 expression.
Keyword
Gastric cancer riskMinisatelliteMUC6Polymorphism
ISSN
1059-7794
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/humu.21289
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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