The National Institutes of Health (NIH), through the National Cancer Institute (NCI), has reissued its funding opportunity for epidemiologic research on emerging risk factors and liver cancer susceptibility under the R01 grant mechanism. This program invites proposals focused on novel and established risk factors contributing to liver cancer incidence and aims to enhance understanding of the disease’s etiology, progression, and prevention strategies in the U.S. Researchers are encouraged to investigate the interplay of biological, environmental, and social factors, expanding on existing knowledge about viral hepatitis and other traditional liver cancer risks.

The program emphasizes population-based research into hepatocellular carcinoma (HCC) and other liver cancer types, such as cholangiocarcinoma, hepatoblastoma, and angiosarcoma. These cancers exhibit distinct epidemiological characteristics, but remain underexplored, particularly in relation to non-viral risk factors. HCC, which accounts for 85-90% of primary liver cancers, is traditionally linked to viral hepatitis, alcohol abuse, and environmental exposures. However, recent studies highlight emerging risks such as obesity, non-alcoholic fatty liver disease (NAFLD), diabetes, metabolic syndrome, and environmental toxins, suggesting that these factors significantly contribute to rising liver cancer rates.

This opportunity seeks to generate new insights by supporting epidemiologic studies examining risk factor interactions, including those involving metabolic disorders, viral infections, host immune responses, and behavioral or social determinants of health. Potential areas of investigation include the roles of NAFLD and non-alcoholic steatohepatitis (NASH) in cancer development, the influence of environmental toxins (e.g., perfluoroalkyl substances), and microbiome-related mechanisms affecting the liver-gut axis. Proposals may also explore disparities in liver cancer incidence and mortality across demographic groups and regions, aiming to identify biomarkers or pharmacologic interventions that may aid in prevention and early detection.

The research supported under this initiative can involve primary and secondary data collection, leveraging existing case-control and cohort studies whenever possible. International collaborations are permitted, provided the research is directly relevant to U.S. populations. The program prohibits the investigation of hepatitis B or C as standalone factors unless the research offers innovative insights beyond established knowledge. Proposals seeking solely to establish new cohort studies or extend follow-ups on existing ones will not be considered responsive.

Award budgets are not capped but must align with the project’s scope and goals. The maximum project period is five years. Applicants are encouraged to submit proposals by the NIH standard deadlines, with the earliest submission date being May 5, 2022. The final deadline for applications is November 6, 2024, following an extension under the updated FOA PA-25-121. All proposals must be submitted electronically via the NIH ASSIST system, Grants.gov, or institutional systems linked to Grants.gov. It is essential to register with relevant systems, such as SAM and eRA Commons, well in advance to ensure timely submission.

The application review process will assess each proposal’s significance, innovation, approach, and investigator qualifications, with attention to both scientific merit and alignment with public health priorities. Successful applicants will receive funding notifications following peer review and advisory council evaluations. Awardees are required to comply with NIH policies regarding data sharing, biospecimen use, and civil rights obligations, including accessibility and non-discrimination.

This funding opportunity provides an important platform for advancing knowledge on liver cancer risk factors and contributing to public health strategies aimed at mitigating the disease’s rising incidence in the United States.