Background: Previously, we identified eight novel minisatellites in the MUC2, of which allelic variants in MUC2-MS6 were examined to influence susceptibility to gastric cancer. However, studies on the susceptibility to gastrointestinal cancer of other minisatellites in the MUC2 region still remain unprogressive.
Objective: In this study, we investigated whether polymorphic variations in the MUC2-MS8 region are related to susceptibility to gastrointestinal cancer.
Methods: We assessed the association between MUC2-MS8 and gastrointestinal cancers by a case-control study with 1229 controls, 486 gastric cancer cases, 220 colon cancer cases and 278 rectal cancer cases. To investigate whether intronic minisatellites affect gene expression, various minisatellites were inserted into the luciferase-reporter vector and their expression levels were examined. We also examined the length of MUC2-MS8 alleles in blood and cancer tissue matching samples of 107 gastric cancer patients, 125 colon cancer patients, and 85 rectal cancer patients, and investigated whether the repeat sequence affects genome instability.
Results: A statistically significant association was identified between rare MUC2-MS8 alleles and the occurrence of rectal cancer: odds ratio (OR), 6.66; 95% confidence interval (CI), 1.11-39.96; and P = 0.0165. In the younger group (age, < 55), rare alleles were significant associated with an increased risk of rectal cancer (odds ratio, 24.93 and P = 0.0001). Suppression of expression was found in the reporter vector inserted with minisatellites, and loss of heterozygosity (LOH) of the MUC2-MS8 region was confirmed in cancer tissues of gastrointestinal cancer patients (0.8-5.9%).
Conclusion: Our results suggest that the rare alleles of MUC2-MS8 could be used to identify the risk of rectal cancer and that this repeat region is related to genomic instability.
Keywords: LOH; MUC2; Rectal cancer risk; VNTR.
© 2021. The Genetics Society of Korea.