• APC Mutation Type as a Prognostic Indicator for Tumor Stage in a Iranian Familial Colorectal Cancer Cohort
  • Ali Zarei,1,* Majid Abdollahi,2 Abolfazl Khalafi-nezhad,3 Sara Senemar,4
    1. Department of Human Genetics, Iranian Academic Center for Education, Culture and Research (ACECR)-Fars Branch Institute for Human Genetics Research, Shiraz, Iran
    2. Department of Oncosurgery, Gerash University of Medical Sciences, Gerash, Iran
    3. Hematology Research Center, Department of Hematology, Medical Oncology and Stem Cell Transplantation, Shiraz University of Medical Sciences, Shiraz, Iran
    4. Department of Human Genetics, Iranian Academic Center for Education, Culture and Research (ACECR)-Fars Branch Institute for Human Genetics Research, Shiraz, Iran


  • Introduction: Germline mutations in the Adenomatous Polyposis Coli (APC) gene are a established cause of familial colorectal cancer (CRC). However, the relationship between the type of APC mutation and clinical disease severity, especially within specific ethnic populations like Iranians, is not well defined.
  • Methods: We performed targeted sequencing of the APC Mutation Cluster Region (MCR) in a cohort of 96 Iranian patients with familial CRC, alongside control groups. Identified variants were classified according to ACMG guidelines. Patients were categorized based on their genetic findings, and these categories were statistically evaluated for associations with key clinicopathological parameters, including tumor stage.
  • Results: Pathogenic APC mutations were identified in a significant proportion of patients compared to controls (p<0.0001). Our analysis revealed a highly significant association between the type of APC mutation and advanced tumor stage (p=0.001). Patients harboring truncating pathogenic/likely pathogenic mutations demonstrated a markedly increased prevalence of advanced-stage (III/IV) disease and a significantly higher odds ratio for advanced stage compared to patients with wild-type APC.
  • Conclusion: This study demonstrates that the specific type of APC germline mutation, particularly truncating variants, is a strong biomarker for advanced tumor stage in Iranian patients with familial CRC. These findings highlight the critical importance of incorporating genotypic data into clinical risk stratification strategies for affected families.
  • Keywords: APC gene, Familial Colorectal Cancer, Truncating Mutation, Tumor Stage, Prognostic Biomarker, Iran.