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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

青少年和年轻人（AYA）癌症健康差异的社会基因组机制幸存者。在青春期或成年早期诊断出的癌症幸存者的多种健康风险较高问题。他们还经历了特定且独特的心理社会压力和生活干扰对他们的健康、心理健康和生活质量 (QOL) 的影响。这些结果以及这些结果中的差异结果（按种族/民族、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（包括生物影响）知之甚少。社会环境风险因素对人口健康和福祉的已知影响的途径影响 AYA 癌症幸存者治疗后的结果，特别是发病率、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当前和过去的社会心理和社会环境风险和复原力因素通过哪些因素影响基因 AYA 中的监管，从而有助于更好地了解治疗后的健康差异生存。我们提议对 2000 名 AYA 癌症幸存者进行一项为期 5 年的纵向前瞻性队列研究霍奇金或非霍奇金淋巴瘤治疗完成后一年内。使用重复风险和复原力因素以及血液检测的测量，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，并有可能预测这些指标完成治疗后两年内的癌症幸存者。与东部合作社合作肿瘤学组-美国放射影像学院网络 (ECOG-ACRIN) 研究基础设施和美国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（即不利的生活条件/贫困、童年创伤暴露、社会孤立和歧视）并定义这些基因组的关系 AYA 幸存者死亡率、发病率和生活质量概况； 2）确定全基因组转录影响个人弹性因素（即社会支持、目的感/意义创造、自我效能）并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；并且，3）识别基因组- 弱势群体的广泛分子相关性，如种族/民族、性/性别认同和地理（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。研究结果可能会为新生物/新生物的概念化和开发提供信息。未来干预措施的分子目标，以降低治疗长期和后期影响的风险，并最大限度地提高治疗效果 AYA 癌症幸存者长期健康和生活质量的可能性。