title: Rare exonic minisatellite alleles in MUC2 influence susceptibility to gastric carcinoma.
abstract: BACKGROUND
  Mucins are the major components of mucus and their genes share a common, centrally-located region of sequence that encodes tandem repeats. Mucins are well known genes with respect to their specific expression levels; however, their genomic levels are unclear because of complex genomic properties. In this study, we identified eight novel minisatellites from the entire MUC2 region and investigated how allelic variation in these minisatellites may affect susceptibility to gastrointestinal cancer.
  
  
  RESULTS
  We analyzed genomic DNA from the blood of normal healthy individuals and multi-generational family groups. Six of the eight minisatellites exhibited polymorphism and were transmitted meiotically in seven families, following Mendelian inheritance. Furthermore, a case-control study was performed that compared genomic DNA from 457 cancer-free controls with DNA from individuals with gastric (455), colon (192) and rectal (271) cancers. A statistically significant association was identified between rare exonic MUC2-MS6 alleles and the occurrence of gastric cancer: odds ratio (OR), 2.56; 95% confidence interval (CI), 1.31-5.04; and p = 0.0047. We focused on an association between rare alleles and gastric cancer. Rare alleles were divided into short (40, 43 and 44) and long (47, 50 and 54), according to their TR (tandem repeats) lengths. Interestingly, short rare alleles were associated with gastric cancer (OR = 5.6, 95% CI: 1.93-16.42; p = 0.00036). Moreover, hypervariable MUC2 minisatellites were analyzed in matched blood and cancer tissue from 28 patients with gastric cancer and in 4 cases of MUC2-MS2, minisatellites were found to have undergone rearrangement.
  
  
  CONCLUSIONS
  Our observations suggest that the short rare MUC2-MS6 alleles could function as identifiers for risk of gastric cancer. Additionally, we suggest that minisatellite instability might be associated with MUC2 function in cancer cells.
authors.affiliation: Department of Biological Science, Dong-A University, Busan, Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Jeong
authors.forename: Min Chan
authors.initials: MC
authors.lastname: Kim
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Ahn
authors.forename: So-Young
authors.initials: SY
authors.lastname: Seol
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Do
authors.forename: Hong-Jo
authors.initials: HJ
authors.lastname: Choi
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Chu
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Kim
authors.forename: Yangil
authors.initials: Y
authors.lastname: Sunwoo
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Leem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D004276:DNA, Satellite / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D055262:Mucin-2; D009077:Mucins / Q000235:genetics*; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004276:DNA, Satellite; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins