Social genomic mechanisms of health disparities among Adolescent and Young Adult (AYA) cancer survivors

青少年和青年（AYA）癌症幸存者健康差异的社会基因组机制

• 批准号: 10487418
• 负责人: Bradley Jay Zebrack
• 金额: $ 89.83万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487418
• 关键词: Address; Adolescence; Adolescent and Young Adult; Adult Lymphoma; Affect; Aftercare; Age; American College of Radiology Imaging Network; Antiviral resistance; Biological; Biological Assay; Biology; Blood; Blood specimen; Cancer Model; Cancer Survivor; Cancer Survivorship; Caring; Cells; Childhood; Chronic Disease; Collaborations; Community Clinical Oncology Program; Coping Behavior; Data; Data Set; Development; Discrimination; Disease Progression; Eastern Cooperative Oncology Group; Endocrine; Environmental Risk Factor; Ethnic Origin; Exposure to; Fibrinogen; Future; Gender; Gender Identity; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Geographic Locations; Geography; Goals; Health; Heterogeneity; Hodgkin Disease; Human; Immune; Individual; Inflammation; Inflammatory; Interferon Type I; Intervention; Investigation; Late Effects; Life; Literature; Long-Term Effects; Longitudinal cohort study; Malignant Neoplasms; Maps; Measures; Medical; Mental Health; Molecular; Molecular Target; Morbidity - disease rate; National Cancer Institute; Neoplasm Metastasis; Non-Hodgkin' s Lymphoma; Oncology; Outcome; Pathway interactions; Patients; Personal Satisfaction; Population; Positioning Attribute; Poverty; Process; Prospective cohort study; Psychological Factors; Quality of life; Race; Reporting; Research; Research Infrastructure; Risk; Risk Factors; Role; Rural; Self Efficacy; Social Conditions; Social Environment; Social Functioning; Social isolation; Social support; Structure; Supportive care; Survivors; Symptoms; Treatment/Psychosocial Effects; Tumor Tissue; Vulnerable Populations; Work; adolescent health outcomes; base; cancer diagnosis; cancer recurrence; cancer therapy; childhood adversity; early childhood; experience; functional genomics; genome-wide; genomic profiles; health disparity; immune function; improved; knowledge base; mortality; novel; pediatric trauma; perceived discrimination; physical conditioning; population health; programs; psychologic; psychosocial; psychosocial stressors; recruit; relating to nervous system; resilience; response; sex; social; social engagement; social factors; social genomics; social health determinants; socioeconomic disadvantage; socioeconomics; survivorship; therapy resistant; transcriptome; trauma exposure; treatment effect; tumor progression; young adult

Social genomic mechanisms of health disparities among Adolescent and Young Adult (AYA) cancer survivors. Survivors of cancer diagnosed in adolescence or young adulthood have an elevated risk of multiple health problems. They also experience specific and unique psychosocial stressors and life disruptions having ramifications for their health, mental health, and quality of life (QOL). These outcomes, and disparities in these outcomes (by race/ethnicity, sex and gender, geographic location), may be partially a function of social determinants of health, including socioeconomic gradients, exposures to early childhood traumas or adversity, and accumulated experiences of discrimination. Yet, little is known about these effects including the biological pathways through which the known effects of social-environmental risk factors on population health and well- being influence outcomes in post-treatment AYA cancer survivors, particularly with regard to morbidity, mortality, and QOL. Therefore, the research proposed here is intended to identify and define functional genomic pathways through which current and past psychosocial and social environmental risk and resilience factors influence gene regulation in AYAs, and thus contribute to a greater understanding of health disparities in post-treatment survivorship. We propose a 5-year longitudinal prospective cohort study of 2000 AYA cancer survivors recruited within one year following completion of treatment for Hodgkin or non-Hodgkin lymphomas. Using repeated measures of risk and resilience factors and blood assays, we will evaluate the extent to which biological, psychological and social indicators are associated with, and potentially predict, mortality and morbidity in AYA cancer survivors within two years following completion of therapy. In collaboration with the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) research infrastructure and the National Cancer Institute Community Oncology Research Program (NCORP), this study will 1) identify the genome-wide transcriptional impact of social-environmental RISK factors (i.e., adverse living conditions/poverty, childhood trauma exposure, social isolation, and discrimination) and define the relationships of those genomic profiles to AYA survivor mortality, morbidity, and QOL; 2) identify the genome-wide transcriptional impact of individual RESILIENCE factors (i.e., social support, sense of purpose/meaning-making, self-efficacy) and define the relationships of those genomic profiles to AYA mortality, morbidity, and QOL; and, 3) identify the genome- wide molecular correlates of vulnerable populations, as structured by race/ethnicity, sexual/gender identity, and geography (e.g., rural vs. urban), and define the relationships of those genomic profiles to AYA survivor mortality, morbidity, and QOL. The study results may inform the conceptualization and development of new biological / molecular targets for future interventions to reduce risks for long-term and late effects of treatment and maximize likelihood of long-term health and QOL for AYA cancer survivors.

青少年和年轻成人（AYA）癌症之间健康差异的社会基因组机制 幸存者 在青春期或青年期诊断出的癌症幸存者， 问题他们还经历了具体和独特的心理压力和生活中断， 对他们的健康，心理健康和生活质量（QOL）的影响。这些结果，以及这些差异 结果（按种族/民族、性别和性别、地理位置），可能部分是社会因素的函数。 健康的决定因素，包括社会经济梯度、幼儿期遭受创伤或逆境的情况， 积累了歧视的经验。然而，人们对这些影响知之甚少， 社会环境风险因素对人口健康和健康的已知影响的途径， 影响治疗后AYA癌症幸存者的结局，特别是在发病率，死亡率， 和QOL。因此，本研究旨在确定和定义功能性基因组通路 当前和过去的心理社会和社会环境风险和恢复力因素通过这些因素影响基因 AYAs的监管，从而有助于更好地了解治疗后的健康差异 生存。我们提出了一个为期5年的纵向前瞻性队列研究2000年AYA癌症幸存者招募 在完成霍奇金或非霍奇金淋巴瘤治疗后一年内。使用重复 风险和弹性因素的措施和血液化验，我们将评估生物， 心理和社会指标与AYA的死亡率和发病率相关，并可能预测死亡率和发病率 在完成治疗后两年内的癌症幸存者。与东方合作社合作 肿瘤学组-美国放射学院成像网络（ECOG-ACRIN）研究基础设施和 国家癌症研究所社区肿瘤学研究计划（NCORP），这项研究将1）确定 社会环境风险因素的全基因组转录影响（即，恶劣的生活条件/贫困， 儿童创伤暴露，社会孤立和歧视），并确定这些基因组之间的关系 对AYA幸存者死亡率、发病率和QOL的影响; 2）确定 个体弹性因素（即，社会支持、目的/意义感、自我效能感）和定义 这些基因组图谱与AYA死亡率、发病率和QOL的关系;以及，3）确定基因组- 弱势群体的广泛分子相关性，如种族/民族，性/性别认同，以及 地理（例如，农村与城市），并确定这些基因组图谱与AYA幸存者死亡率的关系， 发病率和QOL。研究结果可能会为新的生物/ 未来干预措施的分子靶点，以降低治疗的长期和迟发效应风险， AYA癌症幸存者的长期健康和生活质量的可能性。