Social Environmental Factors, DNA methylation of inflammation genes and Breast Cancer Survivorship among African American Women

癌症差异可能是由生物、行为和社会环境因素造成的。这个职业 发展提案（CDP）将使杰西·普拉斯卡克博士成为NIH的长期目标得以实现， 受资助的独立研究人员研究社会环境，生物因素和 癌症差异申请人以前的培训包括癌症的社会和空间流行病学 差距。Plascak博士调查了邻里隔离（种族-民族和种族隔离）之间的关系。 社会经济学），社会凝聚力（邻里之间的积极关系），邻里障碍（身体 恶化或缺乏社会控制），歧视和癌症结果。实现跨学科和 独立的癌症差异研究计划将需要以下额外的培训和导师：（1） 癌症分子生物学-遗传学和表观遗传学（Kitaw Demissie和Helmut Zarbl博士），（2）反事实- 基于因果推理（Zhiqiang Tan和Mario Schootman博士），（3）非裔美国人（AA）乳腺癌 （BrCa）流行病学（Elisa Bandera博士），以及（4）社会环境的系统社会观察（SSO） (Drs. Andrew Rundle和Mario Schootman）。Plascak博士将应用这种指导性培训来解决一系列 使用纵向妇女健康圈随访研究（WCHS-L）（R 01 CA 185623）的研究问题 - 一项正在进行的研究招募了1,700名AA BrCa幸存者，并提供了全面的问卷调查数据，包括 知觉邻里社会凝聚力，知觉邻里障碍，医疗记录，癌症登记 记录和血样炎症相关基因的DNA甲基化（DNAm）将从 血液样本将进行SSO，以创建每个WCHS的邻里混乱的客观衡量标准- 参与者的住所。居住隔离措施将从代表以下数据集计算： 研究区域住户的空间分布和社会人口构成。因果推理方法 将用于测试社会环境因素，DNAm和BrCa生存之间的关系。研究 目的是评估：（1）使用SSO评估被试的客观邻里障碍，并探讨相关性 社会环境因素（居住隔离，感知和客观的邻里关系障碍， 社会凝聚力），（2）社会环境因素和BrCa生存之间的关联，以及（3）是否 异常的DNAm和炎症相关基因表达的改变介导了 环境因素和BrCa生存。培训和研究活动已针对罗格斯大学 大学特殊的研究环境：新泽西癌症研究所（NCI综合癌症 中心住房SEER登记）和中心环境暴露和疾病（NIEHS P30中心）。 初步调查结果将构成R 01赠款提案的基础。完成本CDP中概述的活动 将使Plascak博士成为一名独立的、跨学科的癌症差异研究者; 通过预防和控制癌症和癌症差异来改善人口健康。

Cancer disparities might result from biologic, behavioral, and social environmental factors. This Career Development Proposal (CDP) will enable attainment of Dr. Jesse Plascak's long-term goal of becoming an NIH- funded independent investigator studying relationships between the social environment, biologic factors, and cancer disparities. The applicant's previous training includes social and spatial epidemiology of cancer disparities. Dr. Plascak has investigated relationships between neighborhood segregation (racial-ethnic and socioeconomic), social cohesion (positive relationships within neighborhoods), neighborhood disorder (physical deterioration or lack of social control), discrimination, and cancer outcomes. Attaining a trans-disciplinary and independent cancer disparities research program will require the following additional training and mentors: (1) cancer molecular biology – genetics and epigenetics (Drs. Kitaw Demissie and Helmut Zarbl), (2) counterfactual- based causal inference (Drs. Zhiqiang Tan and Mario Schootman), (3) African American (AA) breast cancer (BrCa) epidemiology (Dr. Elisa Bandera), and (4) systematic social observation (SSO) of the social environment (Drs. Andrew Rundle and Mario Schootman). Dr. Plascak will apply this mentored training to address a series of research questions using the longitudinal Women's Circle of Health Follow-up Study (WCHS-L) (R01CA185623) – an ongoing study enrolling 1,700 AA BrCa survivors with comprehensive questionnaire data including perceived neighborhood social cohesion, perceived neighborhood disorder, medical records, cancer registry records, and blood samples. DNA methylation (DNAm) of inflammation-related genes will be quantified from blood samples. SSO will be conducted to create objective measures of neighborhood disorder of each WCHS- L participant's residence. Residential segregation measures will be calculated from a dataset representative of the spatial distribution and sociodemographic composition of study area households. Causal inference methods will be used to test relationships between social environmental factors, DNAm, and BrCa survival. The research aims are to assess: (1) participants' objective neighborhood disorder using SSO and investigate correlations between social environmental factors (residential segregation, perceived and objective neighborhood disorder, social cohesion), (2) associations between social environmental factors and BrCa survival, and (3) whether aberrant DNAm and altered expression of inflammation-related genes mediate the association between environmental factors and BrCa survival. Training and research activities have been tailored to the Rutgers University exceptional research environment: The Cancer Institute of New Jersey (NCI Comprehensive Cancer Center housing a SEER registry) and Center for Environmental Exposures and Disease (NIEHS P30 center). Preliminary findings will form the basis of a R01 grant proposal. Completion of the activities outlined in this CDP will allow Dr. Plascak to become an independent, transdisciplinary investigator of cancer disparities; contributing to improvements in population health through the prevention and control of cancer and cancer disparities.