Disparities in Colorectal Cancer: Measuring Spatial Accessibility, Screening, and Surveillance Outcomes in South Carolina

The purpose of this dissertation project is to add to the growing literature about the multi-faceted aspects of colorectal cancer (CRC) prevention and related disparities. We focused on the spatial distribution of facilities performing screening services to identify areas that underutilize colonoscopy screening. Next, we examined how the food and physical activity environment affects precursors of CRC by considering plausible pathways. Finally, we explored if access to health insurance reduced the racial disparity of receiving a timely surveillance colonoscopy after a CRC diagnosis. We utilized the SC Ambulatory Surgery Discharge Database, an all-payer, population-based outpatient dataset with colonoscopy records from 2000 – 2014. To identify individuals with a personal history of CRC, we used the SC Central Cancer Registry. We used the Colorectal Cancer Prevention Network screening cohort of low-income, uninsured adults in SC to study colorectal polyps. We paired these unique datasets with innovative analysis methods like two-stage Bayesian hierarchical logistic regression, causal mediation analysis, and loglinear regression. We were able to create catchment areas (CAs) for all facilities in SC performing screening colonoscopies and found that only a small proportion of ZIP codes were not included in any CA. Aspects of the food and physical activity environment had a direct, protective effect on having high-risk colorectal polyps. Finally, we found that over time, increased access to health insurance helped to diminish the racial disparity in receiving a timely surveillance colonoscopy. Overall, this dissertation was able to address gaps in the literature, particularly providing risk and prevalence estimates for the state of South Carolina (SC). This work lays the foundation for addressing screening and surveillance capacity in SC and understanding the individual role within unhealthy environments

The influence of social networks and the built environment on physical inactivity: A longitudinal study of urban-dwelling adults

Policies targeting the built environment to increase physical activity may be ineffective without considering personal social networks. Physical activity and social network data came from the Montreal Neighborhood Networks and Healthy Aging Panel; built environment measures were from geolocation data on Montreal parks and businesses. Using multilevel logistic regression with repeated physical inactivity measures, we showed that adults with more favorable social network characteristics had lower odds of physical inactivity. Having more physical activity facilities nearby also lowered physical inactivity, but not in socially-isolated adults. Community programs that address social isolation may also benefit efforts to increase physical activity

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium.

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the pregnancy and childhood epigenetics (PACE) consortium

© The Author 2017. Published by Oxford University Press. All rights reserved. Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small ( < 0.2% per BMI unit (1 kg/m 2 ), P < 1.06 × 10 -7 ) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for a6causal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 x 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology