• Unraveling the Molecular Mechanisms Underlying Acute Myeloid Leukemia (AML)
  • Arman Moradi,1,* Golnoosh Moradabasi,2
    1. Department of Cellular and Molecular Biology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran
    2. Department of Cellular and Molecular Biology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran


  • Introduction: Introduction Lynch syndrome, a hereditary condition, plays a significant role in elevating the risk of colorectal cancer and various other cancer types due to mutations in DNA mismatch repair (MMR) genes. These MMR genes are crucial for correcting errors that occur during DNA replication, and their dysfunction can lead to genomic instability, thereby increasing cancer susceptibility. One of the key factors influencing gene expression is DNA methylation, an epigenetic modification that can regulate gene activity without altering the DNA sequence itself. DNA methylation typically acts as a silencing mechanism, turning off genes when methyl groups are added to the DNA molecule. In the context of DNA repair genes, changes in methylation status can affect the cell's ability to repair DNA damage, thus impacting cancer risk. This study aims to investigate the influence of DNA methylation changes in specific DNA repair genes on the risk of colorectal cancer in individuals with Lynch syndrome. We will compare these changes to those observed in a control population that does not have Lynch syndrome, thereby shedding light on the potential role of epigenetic modifications in cancer susceptibility within this high-risk group.
  • Methods: Materials and Methods The study involved a total of 150 participants, consisting of 75 individuals diagnosed with Lynch syndrome and 75 age- and sex-matched controls who did not have Lynch syndrome. The participants included 80 males and 70 females, with an average age of 45 years. DNA samples were obtained from both blood and tumor tissues to ensure comprehensive analysis. To assess the methylation status of specific DNA repair genes, we employed methylation-specific PCR (MSP), a sensitive technique that allows the detection of methylation patterns in DNA. The genes selected for analysis were MLH1, MSH2, and MSH6, which are known to be integral components of the MMR system and have been implicated in Lynch syndrome-associated cancers.
  • Results: Results The study uncovered significant differences in the methylation levels of DNA repair genes between the Lynch syndrome patients and the control group. Among the Lynch syndrome patients, 62 out of 75 exhibited hypermethylation in the MLH1 gene, 58 showed hypermethylation in MSH2, and 54 in MSH6. In contrast, the control population demonstrated markedly lower levels of hypermethylation, with 15 individuals showing hypermethylation in MLH1, 12 in MSH2, and 10 in MSH6. These findings indicate that there is a clear association between increased methylation of these DNA repair genes and the presence of Lynch syndrome.
  • Conclusion: Conclusion Our findings strongly suggest that the hypermethylation of DNA repair genes, particularly MLH1, MSH2, and MSH6, is linked to an elevated risk of colorectal cancer in individuals with Lynch syndrome. The observed epigenetic modifications in these genes could potentially serve as biomarkers for the early detection of cancer risk, facilitating targeted prevention strategies for this vulnerable population. Identifying and understanding these methylation patterns may offer new insights into the mechanisms underlying Lynch syndrome and contribute to the development of personalized therapeutic approaches aimed at mitigating cancer risk in affected individuals.
  • Keywords: Lynch syndrome, colorectal cancer, DNA methylation, DNA repair genes, epigenetics