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

项目摘要/摘要 肝细胞癌是美国与癌症相关的死亡上升最快的原因，也是主要的 肝硬变患者的死因。男性受到的影响更大，发病率是男性的2-8倍 在全球范围内，不同时期和所有种族和族裔群体的死亡率和死亡率都高于女性。尽管如此 一致的观察，性(即，生物)和与性别(即，社会，行为)相关的程度 造成肝细胞癌风险和存活率差异的因素尚不清楚。此外，肝细胞癌中的性别差异 肝硬变患者的发病率还有待调查--这是美国的主要高危人群。 应用程序采用沃内克概念模型来阐明特定的性别因素和与性别相关的因素 以前还没有研究过肝细胞癌的差异。然后将该模型应用于3个大型多中心 所有这些患者都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，肝癌风险的差异主要受性别相关生物因素的影响， 而肝细胞癌存活率的差异在更大程度上是由性别相关的社会和行为驱动的 因素，将通过以下具体目标进行调查：1)估计性别之间的联系- 4,000例肝硬变患者的相关因素和肝细胞癌风险；2)量化生存的大小 3)评价性别因素和性别相关因素对肝癌的影响。 肝细胞癌存活率。来自AIMS项目的数据将被三角测量，以提供干预措施以减少 肝细胞癌。PI是德克萨斯大学西南分校的临床研究员和肝病专家，他有长期的解决方案 癌症健康差异和改善对肝细胞癌患者的护理。拟议的培训计划是综合的 研究的目的和基础是她在临床研究和流行病学方面的现有知识。她有 组建了一支才华横溢、专业互补的跨学科导师团队：阿米特博士 Singal，经验丰富的健康服务研究员和内容专家；Carolyn Mazure博士，国际 性别和性别对健康影响研究的公认专家；凯瑟琳·麦格林博士， 在癌症性激素方面拥有专业知识的流行病学家；以及行为科学家Jasmin Tiro博士 混合方法研究方面的专业知识。PI将获得新的、先进的技能来理解影响 关于健康中的性别和性别、高级量化分析、混合方法研究和知识 综合为干预发展提供信息。这项提案中的研究研究具有重要的公开性 对健康的影响，因为它们将填补我们对性别和性别对肝细胞癌差异影响的理解的空白 并扩大女性对肝癌的了解，这是一个在肝癌研究中代表性不足的人群。本奖项 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，专注于减少肝病患者的健康差距 疾病和肝癌。

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.