Epigenetic modification and risk of Hepatocellular carcinoma in high incidence region of Northeast India

Hepatocellular carcinoma (HCC) is a leading liver cancer globally, with Northeast India reporting particularly high incidence rates according to Population-Based Cancer Registry (PBCR) data. Despite its prevalence, the role of epigenetic changes, especially DNA methylation, in HCC development in this region remains underexplored. Aberrant DNA methylation patterns offer significant potential as biomarkers for diagnosing and monitoring individuals at high risk. This study focuses on understanding the contribution of DNA methylation to HCC pathogenesis in two states of Northeast India, aiming to provide insights into disease mechanisms and improve early detection strategies in this high-risk population. A population-based case-control study was conducted in Arunachal and Sikkim, two states of North-eastern India, involving a total of 164 participants of HCC (73 histologically-confirmed cases, 91 age and sex-matched controls), with blood samples collected and analyzed for methylation patterns in four key tumor suppressor and DNA repair genes: p16, APC, GSTP1, and MGMT. The findings reveal that methylation was observed in a subset of liver cancer patients, with the highest prevalence in the p16 gene (5 cases) followed by APC, MGMT, and GSTP1. Epidemiological analysis highlighted significant associations between HCC risk and factors such as male predominance, lower literacy levels, alcohol use, and chronic hepatitis B (HBV) or hepatitis C (HCV) infections. This study emphasizes the critical role of epigenetic modifications in HCC pathogenesis and suggests that DNA methylation in tumor suppressor and DNA repair genes could serve as potential biomarkers for early detection and risk assessment of HCC in Northeast India.