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  • The Role of Epigenetics in the Prevention and Treatment of Hereditary Colorectal Cancer through Nutrition and Targeted Therapies.

  • Mobina Hassanzadeh Aliabadi,1,*
    1. Institute of Converging Sciences and Technologies ,SR.C., Islamic Azad University, Tehran, Iran


  • Introduction: Epigenetic studies have elucidated the dynamic relationship between nutrition and food quality control. Changes in gene expression without regulation of the DNA sequence are considered potentially reversible and, unlike intrinsic genetic alterations in cancer, offer targets for treatment and prevention. Epigenetic alterations, including histone modifications, changes in chromatin structure, DNA methylation, and ncRNA expression, have been identified as significant factors in the pathogenesis of colorectal cancer (CRC). Diet and lifestyle play a role in the prevention of this cancer. High-fat and unhealthy diets alter the gut microbiome and promote cancer development. CRC is also caused by some carcinogens, which damage DNA and disrupt cell structure. Carcinogens include chemicals, processed meats containing nitrates and nitrites, and natural toxins such as pesticides, which are associated with an increased risk. Today, surgery, chemotherapy, radiotherapy, and epidrugs (epigenetic drugs) are used to treat cancer. Drugs are known as targeted therapies and block specific molecules involved in cancer growth. Epigenetic targeted therapies, including inhibitors of DNA methyltransferases and histone deacetylases, hold promise for improved treatment. Dietary interventions, including dietary fibre, and micronutrients such as calcium, protein, selenium, and vitamins, are helpful in the treatment of CRC (Pillai, Mendhe et al. 2024) DNA methylation is an epigenetic regulation that regulates gene expression by adding a methyl group to a CpG site through the action of the enzyme DNMT. In contrast, DNMT3A/B is known as a de novo methyltransferase because it produces new methylation marks on CpG dinucleotides, which are very important in the early stages of development. Epigenetic control is mediated by ncRNAs, including miRNAs and lncRNAs, which are encoded in the genome. These ncRNAs play a role in carcinogenesis and tumour suppression, making them suitable targets for targeted therapy due to their variable expression in cancers. (Marei 2025) miR-21 is involved in increasing tumour invasion and growth, while miR-145 is involved in suppressing cell invasion and migration. LncRNAs, such as H19, CRNDE, and CCAT1, are upregulated in CRC and contribute to the activation of the Wnt/β-Catenin pathway, ultimately leading to tumour genesis. Exercise is another environmental epigenetic factor that protects against CRC through biological mechanisms such as reducing inflammation, improving immune function, and creating beneficial epigenetic changes. High-intensity physical activity helps regulate hormones, such as insulin and insulin-like growth factors (IGFs), and exhibits additional protective effects. (Sun, Keat et al. 2025) Lynch syndrome (LS) is a genetic mutation or epigenetic alteration in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. In LS patients, there is an increased risk of CRC until the age of seventy. There are tests for diagnosing CRC, including IHC and MSI, and it can also be detected through NGS. (Dal Buono, Puccini et al. 2024) In CRC, methylation of the MLH1 gene promoter is detected using methylation-sensitive Pyrosequencing for diagnostic and prognostic purposes. (Montgomery and Srinivasan 2019) . An imbalance between histone deacetylases (HDACs) and histone acetyltransferases (HATs) leads to altered gene expression and cancer progression. Epigenetic inhibitors such as RG108, MG98, Psammaplin, and Aza-cdr-5 are used to correct DNA and histone methylation changes in CRC. Combinations of two or more drugs target epigenetic events. Their clinical application has progressed rapidly, leading to the development and approval of targeted epigenetic therapies, as well as epigenetic drugs. (Song, Yang et al. 2025) Drugs such as Azacitidine and Decitabine are approved for use in haematological malignancies and are under investigation for patients with solid tumours such as CRC. (Suraweera, O'Byrne et al. 2025)
  • Methods: I have written a review article and it dose not have materials and methods .
  • Results: I have written a review article and it dose not have results .
  • Conclusion: Epigenetics plays an essential role in the pathogenesis and treatment of colorectal cancer. Genetic alterations, epigenetic changes, are reversible and can be modulated by nutrition, exercise, and targeted drugs (epidrugs). Unhealthy diet, alterations, and changes in ncRNAs (such as miR-21 and lncRNAs) play a role in tumorigenesis. Epigenetic drugs such as Azacitidine and Decitabine are being investigated for the treatment of CRC, but they still have challenges in solid tumours. Combining drug therapies with a healthy lifestyle is observational and promising.
  • Keywords: Colorectal Cancer (CRC) Epigenetic Regulation, DNA Methylation , ncRNAs ,Epigenetic Drugs

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