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Rare minisatellite alleles of MUC2-MS8 influence susceptibility to rectal carcinoma

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Abstract

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.

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Acknowledgements

We sincerely appreciate the many patients and individuals who participated in this study.

Funding

This work was supported by the Dong-A University research fund.

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Author notes

  1. So-Young Seol and Gi-Eun Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of Biomedical Science, Dong-A University, Busan, 49315, Korea

    So-Young Seol, Gi-Eun Yang, Yoon Cho & Sun-Hee Leem

  2. Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul, Korea

    So-Young Seol

  3. Department of Health Sciences, Dong-A University, Busan, 49315, Korea

    Gi-Eun Yang, Yoon Cho & Sun-Hee Leem

  4. Department of Surgery, College of Medicine, Dong-A University, Busan, 49201, Korea

    Min Chan Kim & Hong-Jo Choi

  5. Department of Biochemistry, College of Oriental Medicine, Anti-Aging Research Center, Dong-Eui University, Busan, 47227, Korea

    Yung Hyun Choi

Authors
  1. So-Young Seol
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  2. Gi-Eun Yang
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  3. Yoon Cho
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  4. Min Chan Kim
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Corresponding author

Correspondence to Sun-Hee Leem.

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Conflict of interest

So-Young Seol, Gi-Eun Yang, Yoon Cho, Min Chan Kim, Hong-Jo Choi, Yung Hyun Choi, and Sun-Hee Leem declare that they have no conflict of interest.

Ethical approval

This study was approved by the Board for Ethics in Medical Research, Dong-A University Hospital [#IRB-06-10-02 & #IRB-07-10-7; Busan, Korea] and Chungbuk National University Hospital [#IRB-2006-1; Cheongju, Korea].

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Seol, SY., Yang, GE., Cho, Y. et al. Rare minisatellite alleles of MUC2-MS8 influence susceptibility to rectal carcinoma. Genes Genom 43, 1381–1388 (2021). https://doi.org/10.1007/s13258-021-01158-0

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  • DOI: https://doi.org/10.1007/s13258-021-01158-0

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