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Interrelations of Apoptotic and Cellular Senescence Genes Methylation in Inflammatory Bowel Disease Subtypes and Colorectal Carcinoma in Egyptians Patients

  • Ragaa H. Salama
  • Zain El-Abdeen A. Sayed
  • Ahmed M. Ashmawy
  • Wael A. Elsewify
  • Ghada M. EzzatEmail author
  • Mahmoud A. Mahmoud
  • Aya A. Alsanory
  • Tasneem A. Alsanory
Article
  • 42 Downloads

Abstract

Ras-related domain family member 1 transcript variant A (RASSF1A) controls apoptosis and cell proliferation while p14/ARF gene has a regulatory role in cellular senescence. Failure of apoptosis and cellular senescence occurs during inflammatory bowel disease (IBD) and colorectal cancer (CRC). To reveal the role of peripheral leukocyte promoter methylation of RASSF1A and p14/ARF in the pathogenesis of IBD subtypes and CRC we investigated the methylation state of the two genes by methylation-specific polymerase chain reaction (MSP-PCR) in 60 CRC patients, 60 patients with IBD; 27 with ulcerative colitis and 33 had Crohn’s disease and also in 30 healthy subjects. Methylated RASSF1A and p14/ARF genes were detected in 55% and 60% of CRC, while the frequency of the methylated RASSF1A and p14/ARF genes was 23.3% and 43.3% in IBD patients and 3.3% and 13.3% in the control group (P = 0.000 each). Also, the frequency of methylated RASSF1A gene was significantly higher in ulcerative colitis than in Crohn’s disease, while a non-significant frequency of methylated p14/ARF was detected between ulcerative colitis and Crohn’s disease. Furthermore, methylated RASSF1A and p14/ARF were associated with the grade of CRC but not associated with the age of patients, family history, or tumor location. Results suggest that methylated RASSF1A and p14/ARF are related to CRC and IBD pathogenesis and may be used as molecular biomarkers for early detection of CRC and IBD.

Keywords

RASSF1A p14/ARF Methylation-specific PCR Inflammatory bowel disease Colorectal cancer 

Abbreviations

ARF

alternative reading frame

CDK2

cyclin-dependent kinase-2

CRC

colorectal cancer

IBD

inflammatory bowel disease

MSP-PCR

methylation-specific polymerase chain reaction

RASSF1A

Ras-association domain family 1A.

Notes

Funding information

The study received support from grant office, Faculty of Medicine, Assiut University—grant no. R3-2015.

Compliance with Ethical Standards

The study was approved by the Faculty’s Ethics committee (ethical code, 17100666) and in concordance to Helsinki II declaration. All participants gave informed consent before the study start.

Conflict of Interest

The authors declared that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ragaa H. Salama
    • 1
  • Zain El-Abdeen A. Sayed
    • 2
  • Ahmed M. Ashmawy
    • 2
  • Wael A. Elsewify
    • 3
  • Ghada M. Ezzat
    • 1
    Email author
  • Mahmoud A. Mahmoud
    • 2
  • Aya A. Alsanory
    • 4
  • Tasneem A. Alsanory
    • 4
  1. 1.Department of Medical Biochemistry, Faculty of MedicineAssiut UniversityAssiutEgypt
  2. 2.Department of Internal Medicine, Faculty of MedicineAssiut UniversityAssiutEgypt
  3. 3.Department of Internal Medicine, Faculty of MedicineAswan UniversityAswanEgypt
  4. 4.Students at Faculty of Medicine, Faculty of PharmacyAssiut UniversityAssiutEgypt

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