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.

青春期和青壮年(Aya)癌症健康差异的社会基因组机制 幸存者。 在青春期或青春期被诊断为癌症的幸存者有更高的多重健康风险 有问题。他们还会经历特定和独特的心理社会压力和生活中断 对他们的健康、心理健康和生活质量(QOL)的影响。这些结果，以及这些结果之间的差距 结果(按种族/族裔、性别和性别、地理位置)可能在一定程度上是社会的功能 健康的决定因素，包括社会经济梯度、儿童早期创伤或逆境的暴露， 并积累了歧视的经验。然而，人们对这些影响知之甚少，包括生物学上的 已知的社会环境风险因素对人群健康和健康的影响途径 影响治疗后癌症幸存者的结局，特别是在发病率、死亡率、 和生活质量。因此，这里提出的研究旨在识别和定义功能基因组途径 现在和过去的心理社会和社会环境风险和复原力因素通过什么影响基因 AYA的监管，从而有助于更好地了解治疗后的健康差距 生存能力。我们建议对招募的2000名癌症幸存者进行为期5年的纵向前瞻性队列研究。 在完成霍奇金或非霍奇金淋巴瘤治疗后一年内。使用重复的 风险和复原力因素的衡量以及血液分析，我们将评估生物学、 心理和社会指标与阿亚的死亡率和发病率相关，并有可能预测死亡率和发病率 癌症幸存者在完成治疗后的两年内。与东方合作社合作 肿瘤学小组-美国放射成像学院网络(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(例如，不利的生活条件/贫困， 童年创伤暴露、社会孤立和歧视)，并定义了这些基因组之间的关系 对AYA幸存者死亡率、发病率和生活质量的影响；2)确定AYA对全基因组转录的影响 个人复原力因素(即社会支持、使命感/意义创造、自我效能)和定义 这些基因组图谱与AYA死亡率、发病率和生活质量的关系；以及，3)识别基因组- 弱势群体的广泛分子关联，如种族/族裔、性/性别认同以及 地理位置(例如，农村与城市)，并定义这些基因组图谱与Aya幸存者死亡率的关系， 发病率和生活质量。研究结果可为新生物医学的构思和发展提供参考。 未来干预的分子目标，以降低治疗的长期和晚期影响的风险，并最大限度地提高 Aya癌症幸存者长期健康和生活质量的可能性。