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

项目总结/摘要 肝细胞癌（HCC）是美国癌症相关死亡的最快上升原因，并且是癌症死亡的主要原因。 肝硬化患者的死亡原因。男性受影响的比例更大，发病率高出2-8倍 在全球范围内，在各个时期和所有种族和族裔群体中，妇女的死亡率和死亡率都高于妇女。尽管如此 一致的观察，性别的程度-（即，生物学的）和性别相关的（即，社会的，行为的） 导致HCC风险和生存率差异的因素尚不清楚。此外，HCC中的性别差异 肝硬化患者（美国主要的高危人群）的发病率尚未进行研究。 应用程序采用Warnecke概念模型来阐明特定的性和性别相关因素， 以前没有探讨过HCC中的差异。然后将该模型应用于3个大型多中心 肝硬化和HCC患者队列-所有患者均具有独特的临床和调查数据以及储存的血清样本。 中心假设认为HCC风险的差异主要受性别相关生物因素的影响， 而HCC生存率的差异在很大程度上是由性别相关的社会和行为因素造成的， 将通过以下具体目标进行调查：1）估计性别之间的关联- > 4，000例肝硬化患者的相关因素和HCC风险; 2）量化生存率的大小 男性和女性HCC患者之间的差异; 3）评估性别和性别相关因素对HCC的影响。 HCC生存率。将对项目目标的数据进行三角测量，以便为采取干预措施提供信息， HCC。PI是UT西南大学的临床研究员和肝病学家，具有解决 癌症健康差异和改善HCC患者的护理。拟议的培训计划已整合 与研究目标，并建立在她现有的知识，在临床研究和流行病学。她有 组建了一支才华横溢的跨学科导师团队，他们具有互补的专业知识：Amit博士 Singal，HCC经验丰富的健康服务研究员和内容专家; Carolyn Mazure博士，国际 研究性和性别对健康影响的公认专家;凯瑟琳麦格林博士， 流行病学家，专门研究癌症中的性激素;和Jasmin Tiro博士，行为科学家， 混合方法研究的专业知识。PI将获得新的，先进的技能，了解影响 健康中的性和性别、先进的定量分析、混合方法研究和知识 为制定干预措施提供信息的综合报告。本研究报告中的研究具有重要的公众影响力。 健康影响，因为它们将填补我们对性别和性别对HCC差异影响的理解空白 并扩大对女性HCC的了解，这是HCC研究中代表性不足的人群。这个奖项 职业发展计划将为PI提供受保护的时间，培训，指导和经验 建立一个独立资助的研究事业，专注于减少肝脏疾病患者的健康差异， 疾病和HCC。

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.