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

确定性别和性别对肝细胞癌风险和生存的影响

• 批准号: 10652647
• 负责人: Nicole Elizabeth Rich
• 金额: $ 26.35万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10652647
• 关键词: Accounting; Affect; Age; Alcohol abuse; Androgens; Applications Grants; Articulation; Attitude; Award; Behavior; Behavioral; Biological; Biological Factors; California; Cancer Etiology; Caring; Cause of Death; Cessation of life; Cirrhosis; Clinical; Clinical Data; Clinical Research; Cohort Studies; Data; Databases; Development; Development Plans; Diagnosis; Disparity; Early Detection Research Network; Epidemiologist; Estrogens; Ethnic Origin; Ethnic Population; Etiology; Funding; Future; Gender; Goals; Gonadal Steroid Hormones; Health; Health Services; Health behavior; Household; Incidence; Infrastructure; International; Intervention; Interview; Knowledge; Liver diseases; Malignant Neoplasms; Mentors; Mentorship; Modeling; Nested Case-Control Study; Outcome; Pathogenesis; Patient Care; Patients; Population; Primary carcinoma of the liver cells; Prognosis; Prospective Studies; Prospective cohort; Public Health; Race; Reduce health disparities; Research; Research Methodology; Research Personnel; Risk; Risk Factors; Role; Sampling; Scientist; Serum; Social support; Strategic Planning; Structure; Surveys; Talents; Texas; Time; Training; Tumor stage; Underrepresented Populations; United States National Institutes of Health; Viral hepatitis; Woman; Women' s Health; aged; cancer health disparity; career; career development; caregiving; case control; clinical epidemiology; cohort; coping; data harmonization; disparity reduction; experience; gender disparity; health care service utilization; improved; liver function; men; metabolic-associated fatty liver disease; mortality; multi-ethnic; neoplasm registry; perceived stress; racial population; research study; secondary analysis; sex; sex disparity; skills; social; survival disparity; therapy development; treatment adherence

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.

项目概要/摘要 肝细胞癌 (HCC) 是美国癌症相关死亡上升最快的原因，也是主要的死亡原因 肝硬化患者的死亡原因，男性受到的影响尤为严重，发病率高出 2-8 倍。 尽管如此，在不同时期和所有种族和族裔群体中，全球女性的死亡率和死亡率都高于女性。 一致的观察，性别（即生物）和性别相关（即社会、行为）的程度 导致 HCC 风险和生存差异的因素尚不清楚。此外，HCC 的性别差异尚不清楚。 肝硬化患者（美国主要的高危人群）的发病率尚未得到调查。 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，这些因素 之前尚未探讨过 HCC 的差异，然后将该模型应用于 3 个大型多中心。 肝硬化和肝癌患者队列——所有患者都具有独特的临床和调查数据以及存储的血清样本。 核心假设是 HCC 风险的差异主要受到性别相关的生物因素的影响， 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）估计性别之间的关联 > 4,000 名肝硬化患者的相关因素和 HCC 风险 2) 量化生存率； 3) 评估性别和性别相关因素对 HCC 的影响； 将对来自该项目目标的数据进行三角测量，以便为减少差异的干预措施提供信息。 HCC PI 是 UT Southwestern 的临床研究员和肝病学家，具有长期的参与愿景。 癌症健康差异和改善对 HCC 患者的护理 拟议的培训计划是综合的。 符合研究目标，并建立在她现有的临床研究和流行病学知识的基础上。 组建了一支才华横溢、专业知识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 HCC 内容专家 Carolyn Mazure 博士（国际）； 凯瑟琳·麦格林博士是研究性别和性别对健康影响的公认专家； 流行病学家，具有癌症性激素方面的专业知识；Jasmin Tiro 博士，行为科学家， PI 将获得了解影响力的新的高级技能。 健康中的性别和性别、高级定量分析、混合方法研究和知识 该提案中的研究成果具有重要意义。 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，该群体在 HCC 研究中代表性不足。 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异 疾病和肝癌。