The Impact of DNA Methylation Changes in DNA Repair Genes on the Risk of Colorectal Cancer in Patients with Lynch Syndrome Compared to a Control Population

Lynch syndrome is a hereditary disorder characterized by a significant increase in the risk of developing colorectal cancer and several other types of cancer due to mutations in DNA mismatch repair (MMR) genes. These mutations compromise the body’s ability to correct DNA replication errors, leading to the accumulation of genetic alterations. DNA methylation, an epigenetic modification where methyl groups are added to DNA molecules, can impact gene expression, including those involved in DNA repair mechanisms. This study aims to explore the effects of DNA methylation changes in DNA repair genes on colorectal cancer risk among individuals with Lynch syndrome, as compared to a control group without Lynch syndrome. Materials and Methods: This study included ۱۵۰ participants, divided equally into two groups: ۷۵ individuals diagnosed with Lynch syndrome and ۷۵ age- and sex-matched controls who do not have Lynch syndrome. The cohort consisted of ۸۰ males and ۷۰ females, with an average age of ۴۵ years. DNA was extracted from blood and tumor tissues of participants. To evaluate the methylation status of crucial DNA repair genes, we employed methylation-specific PCR (MSP). This technique allowed us to identify and quantify methylation patterns in the genes of interest, which are critical for maintaining genomic stability. Results: Analysis of the data revealed significant differences in the methylation levels of DNA repair genes between Lynch syndrome patients and the control group. Specifically, ۶۲ out of ۷۵ patients with Lynch syndrome exhibited hypermethylation in the MLH۱ gene, ۵۸ showed hypermethylation in the MSH۲ gene, and ۵۴ in the MSH۶ gene. In contrast, among the control population, hypermethylation was detected in only ۱۵ individuals for MLH۱, ۱۲ for MSH۲, and ۱۰ for MSH۶. These findings highlight a distinct pattern of increased methylation in DNA repair genes in Lynch syndrome patients. Conclusion: The results of this study indicate that elevated methylation of DNA repair genes, notably MLH۱, MSH۲, and MSH۶, is associated with an increased risk of colorectal cancer in individuals with Lynch syndrome. The observed epigenetic modifications could potentially be utilized as biomarkers for the early detection and development of targeted prevention strategies for individuals at high risk of colorectal cancer due to Lynch syndrome.

کلیدواژه ها:

Lynch syndrome ، colorectal cancer ، DNA methylation ، DNA repair genes ، epigenetics