A secreted MUC6 mucin is reported to be expressed highly in the stomach and gall bladder. In previous our study, the five minisatellites were identified and a significant association between MUC6-MS5 alleles and gastric cancer was reported. Because of aberrant MUC6 expression is often found in gastrointestinal diseases, we evaluated a relationship between MUC6-MS5 and susceptibility to colorectal cancers. Case-control study was performed with 1,103 cancer-free controls and 414 rectal cancer cases. A significant association (OR = 2.70) between short rare MUC6-MS5 alleles (7, 9 repeats) and the occurrence of cancer was observed in rectal cancer [95 % confidence interval (CI), 1.12-6.54; p = 0.022]. Furthermore, a comparison by gender showed the differences in the association ratios between rectal cancer and short rare MUC6-MS5 alleles: male, 3.97 (CI: 1.36-11.5; p = 0.006) versus female 0.91 (CI: 0.18-4.75; p = 0.913). We also examined the association according to lymphovascular invasion (LVI). The frequency of LVI positive rectal cancer was increased in short rare allele cases than in the total rectal cases: 16.2 % versus 42.9 %. Therefore, we suggest that the short rare MUC6-MS5 alleles may be related to cancer development in male and these cancer cases may be related the bad prognosis.

The membrane-bound mucins belong to O-glycoproteins family and they are thought to play important biological roles in cell-cell and cell-matrix interactions, in cell signalling and in modulating biological properties of cancer cells. Among them, MUC4 is well characterized and their altered expression in cancer indicates an important role for these membrane-bound mucins in tumour progression and metastasis; however, their genomic levels are unclear because of complex genomic properties. In this study, we identified seven novel minisatellites from the entire MUC4 region and investigated how allelic variation in these minisatellites may affect susceptibility to cancers. We analyzed genomic DNA from the blood of normal healthy individuals and five (MUC4-MS2, MS3, MS4, MS6, MS7) among the seven minisatellites exhibited polymorphism. Furthermore, a case-control study was performed that compared genomic DNA from 351 cancer-free controls with DNA from individuals with 352 gastric cancers. A statistically significant association was identified between long alleles of MUC4-MS3 and the odds of gastric cancer: odds ratio (OR), 1.3; 95% confidence interval (CI), 1.02-1.59; and p = 0.03. Moreover, MUC4-MS3 alleles showed the highest heterozygosity (h = 0.74) among seven minisatellites that may play a role in its chromosomal instability. This idea was examined by comparing the polymorphic alleles of hypervariable MUC4-MS3 minisatellites in the blood and cancer tissues from 36 patients with gastric cancer and 27 patients with liver cancer. The frequency of rearrangement in MUC4-MS3 was shown each as 27% and 11% in gastric and liver cancer tissues. Furthermore, these rearrangements were detected significantly higher in long alleles than in short alleles. These observations suggest that the long MUC4-MS3 alleles could function as identifiers for risk of gastric cancer. Additionally, we suggest that minisatellite instability might be associated with MUC4 function in cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 917.

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