Determining the influence of sex and gender in hepatocellular carcinoma risk and survival

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PROJECT SUMMARY/ABSTRACT Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related death in the U.S. and a leading cause of death in patients with cirrhosis. Men are disproportionately affected, with 2-8 times higher incidence and mortality rates than women globally, across time periods and all racial and ethnic groups. Despite this consistent observation, the extent to which sex- (i.e., biologic) and gender-related (i.e., social, behavioral) factors contribute to disparities in HCC risk and survival are unknown. Further, sex disparities in HCC incidence have yet to be investigated in patients with cirrhosis – the main at-risk cohort in the U.S. This application adapts the Warnecke conceptual model to articulate specific sex- and gender-related factors that have not previously been explored for disparities in HCC. This model is then applied to 3 large multicenter cohorts of patients with cirrhosis and HCC – all with unique clinical and survey data and stored serum samples. The central hypothesis that disparities in HCC risk are primarily influenced by sex-related biologic factors, whereas disparities in HCC survival are driven to a greater extent by gender-related social and behavioral factors, will be investigated through the following Specific Aims: 1) Estimate the association between sex- related factors and HCC risk in >4,000 patients with cirrhosis; 2) Quantify the magnitude of the survival disparity between men and women with HCC; 3) Evaluate the influence of sex- and gender-related factors on HCC survival. Data from the project aims will be triangulated to inform an intervention to reduce disparities in HCC. The PI is a clinical researcher and hepatologist at UT Southwestern, with a long-term vision of tackling cancer health disparities and improving care for patients with HCC. The proposed training plan is integrated with the research aims and builds on her existing knowledge in clinical research and epidemiology. She has assembled an exceptionally talented interdisciplinary team of mentors with complementary expertise: Dr. Amit Singal, experienced health services researcher and content expert in HCC; Dr. Carolyn Mazure, internationally recognized expert in the study of the influence of sex and gender on health; Dr. Katherine McGlynn, epidemiologist with expertise in sex hormones in cancer; and Dr. Jasmin Tiro, behavioral scientist with expertise in mixed methods research. The PI will acquire new, advanced skills in understanding the influence of sex and gender in health, advanced quantitative analyses, mixed methods research, and knowledge synthesis to inform intervention development. The research studies in this proposal have significant public health impact as they will fill gaps in our understanding of the influence of sex and gender on HCC disparities and expand what is known about HCC in women, a population underrepresented in HCC research. This award and career development plan will provide the PI with the protected time, training, mentorship, and experience to build an independently funded research career focused on reducing health disparities in patients with liver disease and HCC.