Hepatocellular carcinoma (HCC), one of the most lethal tumors globally, has long been a research hotspot due to its complex pathogenesis involving interactions between genetics, metabolism, and viral infections. Recently, at the 2025 EASL Liver Cancer Summit held in Paris, France, a study by Professor Mohamed Abdel Samie's team from the Department of Hepatology and Gastroenterology at the National Liver Institute, Menoufia University, Egypt, revealed the crucial role of the HNF1A genotype in HCC risk. Oncology Frontier invited Professor Mohamed Abdel Samie to discuss the potential value of this gene in HCC screening and the impact of metabolic factors. We look forward to future personalized treatment strategies targeting specific genotypes bringing new breakthroughs in the prevention and treatment of HCC.

Oncology Frontier: Your study highlights the role of the HNF1A genotype in the risk of HCC among affected patients. Given the variant genetic backgrounds in different populations, do you think the risk association could differ in other ethnic groups, such as Asian people, where hepatitis B virus (HBV) is more prevalent?

Dr. Mohamed Abdel Samie: Hepatocyte Nuclear Factor 1A (HNF1A) was studied in my research on patients with hepatitis C virus (HCV) as well as in patients with diabetes mellitus. I believe it may also be relevant for patients with diabetes mellitus in China. However, further research is needed to determine its role in HBV-related HCC and to validate our findings in HBV-infected populations.

Oncology Frontier: Your research found that the AA genotype was significantly associated with increased HCC risk. Would you recommend HNF1A genetic testing as part of routine screening for high-risk populations? And if so, how could this be integrated into existing HCC surveillance programs?

Dr. Mohamed Abdel Samie: For genetic testing to be incorporated into HCC surveillance programs, it should be cost-effective and less expensive than other non-invasive markers, such as alpha-fetoprotein (AFP) and ultrasound. However, early detection is crucial for curative therapy, particularly in the early stages of HCC. If genetic testing becomes more accessible, it could play a vital role in identifying high-risk individuals and improving HCC screening strategies.

Oncology Frontier: Diabetes mellitus is increasingly recognized as a co-factor in HCC development. Do you believe lifestyle interventions targeting metabolic factors could modify the genetic risk associated with HNF1A variants, or is the genetic predisposition altered by external factors?

Dr. Mohamed Abdel Samie: Genetic predisposition is influenced by external factors. Our findings indicate that even a single allele of HNF1A may significantly increase the risk of HCC in HCV-positive diabetic patients, as well as in diabetic patients without viral hepatitis. This suggests that genetics play a role, but metabolic and environmental factors are also important. Lifestyle interventions aimed at managing diabetes and metabolic disorders could potentially reduce the impact of HNF1A variants on HCC development.

Oncology Frontier: Considering that China has a high burden of both HCC and HBV, do you see potential for collaborative studies between Egypt and Chinese researchers to validate HNF1A as a biomarker in diverse populations?

Dr. Mohamed Abdel Samie: Yes, collaboration between Egypt and China is essential, given the high prevalence of HBV and HCV in both countries. One of our research objectives is to conduct a large-scale study to validate our findings. The significance of single-gene biomarkers must be confirmed on a broader scale. We welcome joint research projects between Egypt and China to explore the role of HNF1A in HCC risk across different populations.