• Genetic Evaluation of Pancreatic Cancer Development in Individuals with a Congenital Obesity Phenotype in Iran
  • Farzaneh Ramezani Hombari,1,*
    1. Shahid Beheshti University of Medical Sciences, Health Science and Technology Park, West Second Floor, Genomics Research Laboratory


  • Introduction: Pancreatic cancer is one of the most lethal and challenging types of gastrointestinal cancers, often diagnosed at advanced stages and associated with a low five-year survival rate. Identifying risk factors contributing to the development of this disease holds critical clinical and epidemiological importance. One such risk factor is obesity, particularly in the form of congenital genetic obesity phenotypes, which has recently been recognized as a contributor to inflammatory processes, insulin resistance, lipid metabolism disorders, and ultimately the activation of tumorigenic pathways.Recent genetic and epigenetic studies have highlighted the crucial roles of obesity-related genes and single nucleotide polymorphisms (SNPs)—such as FTO, MC4R, LEP, LEPR, and IRS1—and associated signaling pathways, including PI3K/AKT, JAK/STAT, and mTOR, in the progression of pancreatic cancer. The co-occurrence of chronic obesity with a specific genetic background may lead to the stimulation of growth factors, elevated levels of insulin and IGF-1, and the development of a chronic inflammatory state, all of which create a favorable environment for neoplastic cell proliferation.In Iran, despite the high prevalence of obesity in certain local populations, there is limited genetic and bioinformatics-level insight into the association between congenital obesity and the development of pancreatic cancer. This study aims to identify and analyze shared genetic variants between congenital obesity and pancreatic cancer using bioinformatics tools and databases to investigate gene interactions, signaling pathways, and gene expression networks.The findings of this research may enhance our understanding of the shared genetic and molecular mechanisms between obesity and pancreatic cancer and pave the way for identifying biomarkers and novel therapeutic targets within the Iranian population
  • Methods: We conducted this research as a bioinformatics-based study grounded in previous literature and databases, with a focus on genetic variations and epigenetic changes associated with both congenital obesity and pancreatic cancer.Relevant databases used for gene identificationincluded:OMIM,GeneCards,DisGeNET,GWAS Catalog,NCBIEnsemble,KEGGThese resources were used to identify genes associated with congenital obesity and their potential roles in pancreatic cancer.We compiled genetic data and signaling pathway information for both conditions. The KEGG Pathway Database was used as a primary tool for visualizing gene-pathway relationships. Additionally, we performed functional annotation and variant effect analysis using resources such as VEP and SNPnexus.
  • Results: The findings of this study indicate that individuals with a congenital obesity phenotype are genetically predisposed to activating signaling pathways that are also implicated in the pathogenesis of pancreatic cancer. Notably, the PI3K/AKT signaling pathway, which plays a critical role in cell proliferation and resistance to apoptosis, was found to be highly active in both conditions. This suggests that the link between congenital obesity and pancreatic cancer is not solely due to metabolic factors but also reflects shared underlying genetic mechanisms
  • Conclusion: Bioinformatics analysis revealed several common genes and signaling pathways between congenital obesity and pancreatic cancer. The identification of these shared pathways and genes could help in developing predictive biomarkers for pancreatic cancer in obese individuals. Further functional and genotypic studies are recommended, particularly in the Iranian population, to validate these findings and explore clinical applications.
  • Keywords: obesity, bioanformatic ,pancreatic cancer