Rare exonic minisatellite alleles in MUC2 influence susceptibility to gastric carcinoma.
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.
Jeong
Yun Hee
YH
Department of Biological Science, Dong-A University, Busan, Korea.
Kim
Min Chan
MC
Ahn
Eun-Kyung
EK
Seol
So-Young
SY
Do
Eun-Ju
EJ
Choi
Hong-Jo
HJ
Chu
In-Sun
IS
Kim
Wun-Jae
WJ
Kim
Woo Jin
WJ
Sunwoo
Yangil
Y
Leem
Sun-Hee
SH
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*
D017931:DNA Primers; D004276:DNA, Satellite; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins