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.

项目摘要/摘要 肝细胞癌（HCC）是美国与癌症相关死亡的最快崛起的原因，是领先的 肝硬化患者死亡原因。男性受到不成比例的影响，事件高2-8倍 和死亡率比全球，跨越时间以及所有种族和种族群体的女性。尽管如此 一致的观察，性别（即生物学）和与性别有关的程度（即社会，行为） 导致HCC风险差异的因素尚不清楚。此外，HCC中的性别差异 肝硬化患者尚未研究发病率 - 美国的主要高危队列 应用程序适应Warnecke概念模型，以表达特定的性别和与性别相关的因素 以前尚未探索HCC中的分布。然后将该模型应用于3个大型多中心 肝硬化和HCC患者的人群 - 均具有独特的临床和调查数据，并存储了血清样品。 枢纽风险中的分布主要受性别相关的生物学因素的影响， 而与性别相关的社会和行为，HCC生存的差异更大程度地驱动 因素将通过以下特定目的进行研究：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）量化生存的大小 男性和女性与HCC之间的差异； 3）评估性别和性别相关因素对 HCC生存。项目目标的数据将进行三角测量，以告知干预措施以减少分布 HCC。 PI是UT Southwestern的临床研究人员和肝病学家，具有长期愿景 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 这项研究的目的并建立在她在临床研究和流行病学上的现有知识上。她有 组建了一支具有完善专业知识的具有才华横溢的导师跨学科团队：阿米特博士 HCC中的Singal，经验丰富的卫生服务研究人员和内容专家； Carolyn Mazure博士，国际 在研究性别和性别对健康的影响方面的公认专家；凯瑟琳·麦格林博士， 流行病学家在癌症中具有性激素专业知识；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将获得理解影响力的新的高级技能 性别和性别的健康，高级定量分析，混合方法研究和知识 合成以告知干预开发。该提案中的研究有很大的公众 健康影响，因为它们将在我们对性别和性别对HCC差异的影响的理解中填补空白 并扩大女性HCC已知的内容，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职业，重点是减少肝脏患者的健康分布 疾病和HCC。