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.

中文翻译：

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MUC2-MS8 的罕见小卫星等位基因影响直肠癌的易感性

背景

以前，我们在 MUC2 中鉴定了 8 个新的小卫星，其中 MUC2 -MS6中的等位基因变体被检查以影响对胃癌的易感性。然而，关于MUC2区域其他小卫星对胃肠道癌易感性的研究仍然没有进展。

客观的

在这项研究中，我们调查了MUC2 -MS8 区域的多态性变异是否与胃肠道癌的易感性有关。

方法

我们通过一项病例对照研究评估了MUC2 -MS8 与胃肠道癌之间的关联，其中有 1229 例对照、486 例胃癌病例、220 例结肠癌病例和 278 例直肠癌病例。为了研究内含子小卫星是否影响基因表达，将各种小卫星插入荧光素酶报告载体并检查它们的表达水平。我们还检查了107 名胃癌患者、125 名结肠癌患者和 85 名直肠癌患者的血液和癌组织匹配样本中MUC2 -MS8 等位基因的长度，并研究了重复序列是否影响基因组不稳定性。

结果

发现罕见的MUC2 -MS8 等位基因与直肠癌的发生之间存在统计学上显着的关联：优势比 (OR)，6.66；95% 置信区间 (CI)，1.11–39.96；P  = 0.0165 。在较年轻的组（年龄，<55）中，稀有等位基因与直肠癌风险增加显着相关（优势比，24.93 和P  = 0.0001）。在插入小卫星的报告载体中发现表达抑制，并且在胃肠癌患者的癌组织中证实了MUC2 -MS8 区域的杂合性 (LOH) 丢失 (0.8-5.9%)。

结论

我们的研究结果表明，MUC2 -MS8 的稀有等位基因可用于识别直肠癌的风险，并且该重复区域与基因组不稳定性有关。