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

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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.