The National Institutes of Health (NIH), through its National Cancer Institute (NCI), has reissued a funding opportunity titled *Epidemiologic Research on Emerging Risk Factors and Liver Cancer Susceptibility (R21 Clinical Trial Not Allowed)* under announcement number PAR-22-084. This grant is designed to promote exploratory and developmental research investigating new hypotheses on emerging risk factors for liver cancer, particularly hepatocellular carcinoma (HCC) and other histological subtypes like cholangiocarcinoma and hepatoblastoma. The initiative encourages the study of biological, environmental, and social factors, both independently and in conjunction with established risk factors such as viral hepatitis, to better understand the development and rising incidence of liver cancer in the U.S.

The purpose of this funding opportunity is to enhance research that explores novel risk factors and their interactions with established causes of liver cancer, such as hepatitis B and C viruses, alcohol use, and environmental exposures like aflatoxin. The initiative is particularly interested in exploring emerging non-viral risk factors, such as non-alcoholic fatty liver disease (NAFLD), diabetes, obesity, and exposure to toxic substances like poly- and perfluoroalkyl substances (PFAS). Understanding how these factors contribute to liver cancer development will inform prevention strategies. Moreover, the program seeks to investigate the influence of social and geographic disparities on liver cancer incidence and outcomes.

This opportunity is offered under the R21 funding mechanism, which provides up to $275,000 in direct costs for the entire two-year project period, with a maximum of $200,000 allowed per year. It is intended to support early-stage research, which may include pilot projects or studies lacking preliminary data. The goal is to foster the development of new scientific ideas that have the potential for significant impact on liver cancer epidemiology. Eligible applicants include higher education institutions, non-profit organizations, for-profit organizations, government entities, and foreign institutions. Partnerships between U.S. and international researchers are allowed, though the research must directly apply to U.S. liver cancer populations.

To apply, applicants must submit their proposals through the NIH ASSIST system, Grants.gov Workspace, or an institutional system-to-system solution. Proposals must adhere to the instructions provided in the SF424 (R&R) Application Guide, with additional program-specific instructions provided in the announcement. Key dates for submission occur quarterly, starting on June 16, 2022, and extending until November 16, 2024. Applications that do not comply with the specified requirements may be delayed or rejected from review.

Review criteria will focus on the significance, innovation, and approach of the proposed studies, as well as the qualifications of the investigators and the suitability of the research environment. Proposals will be evaluated for their potential to generate new insights into liver cancer risk factors, especially those related to emerging non-viral causes. The involvement of human subjects in the research will require adherence to NIH policies on human subjects protection, data management, and sharing.

In summary, this funding opportunity encourages innovative epidemiologic research to address critical knowledge gaps in liver cancer etiology, particularly concerning non-viral factors. By understanding these emerging risks, researchers can contribute to developing targeted prevention strategies to reduce liver cancer incidence in the U.S. population. Applications are due by the NIH’s standard due dates, and funding decisions will be based on scientific merit, relevance, and available funds.