Investigation of the Methylation Status of Two Autophagy Genes, LC3B and ATG5, with Autophagy Gene Polymorphism ATG16L1 in Patients with Colorectal Cancer in Fars Province
Background:
Colorectal cancer (CRC) is one of the leading causes of death worldwide and is increasingly recognized as a heterogeneous disease at the molecular level. The autophagy-related 5 (ATG5) and light chain 3 (LC3B) genes are involved in the autophagy pathway and play crucial roles in physiological processes, including adaptation to starvation, prevention of neurodegeneration, expression of intracellular antigens, and tumor suppression.
Objectives:
This study aimed to elucidate the epigenetic alterations in the ATG5 and LC3B genes and analyze the polymorphism of ATG16L1 in CRC.
Methods:
This case-control study included 320 blood samples divided into case and control groups, comprising 160 CRC samples and 160 healthy samples. Restriction fragment length polymorphism (RFLP) was used to genotype the ATG16L1 (Thr300Ala) polymorphism, while methylation-specific PCR (MS-PCR) was employed to assess promoter methylation of the ATG5 and LC3B genes. Logistic regression was used to compare methylation patterns and genotypes between case and control groups. Additionally, the chi-square test was applied to compare demographic variables between groups.
Results:
The data analysis revealed a significant difference in the methylation patterns of ATG5 and LC3B between the case and control groups. The promoter methylation status of the LC3B gene candidate region exhibited a lower methylation pattern in the case group (37.3%) compared to the control group (69.4%) (P < 0.001). Conversely, the ATG5 gene promoter showed higher methylation levels in the case group (80.8%) than in the control group (43.8%) (P < 0.001).
Conclusions:
This study analyzed methylation changes in the ATG5 and LC3B genes in CRC patients. The findings suggest that alterations in the promoter methylation patterns of ATG5 and LC3B play significant roles in the pathogenesis of CRC. Additionally, the mutant genotype of ATG16L1 rs2241880 may increase susceptibility to CRC.
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