Project description:Background: Low socioeconomic status (SES) has been linked to chronic stress and poorer health outcomes for marginalized communities in the U.S. The biological processes mediating the impact of SES on health to promote chronic diseases, such as cancer, remain poorly understood. Here, we aim to determine how changes in DNA methylation are linked to neighborhood-level socioeconomic deprivation, thereby promoting cancer initiation and progression through cancer- and immune-related pathways. Methods: We extracted DNA from 402 fresh frozen tissues from 289 women in the NCI-Maryland Breast Cancer Cohort, including 185 tumor samples, 113 additional paired adjacent normal samples, and 104 normal tissues from reduction mammoplasty. Census-tract level socioeconomic deprivation was measured via a Neighborhood Deprivation Index (NDI) using the geocoded addresses from our study participants. DNA methylation values were acquired using the Illumina Infinium MethylationEPIC 850K Beadchip. We conducted a differentially methylated probe (DMP) analysis between tumor and adjacent normal tissue to characterize methylation profiles by NDI status. We also used methylCIBERSORT to estimate immune cell subpopulation differences by tissue type and NDI status. Results: NDI was significantly associated with self-reported race in our cohort in both normal (p<0.0001, 95% CI -4.32, -2.58) and tumor (p<0.0001, 95% CI -4.22, -2.79) tissue. Our DMP analysis showed more significant methylation events (hypo- or hyper- methylation of the tumor tissue compared to adjacent normal tissue) in the NDI high group compared to the NDI low group. We also identified five CpG sites that were significantly hypomethylated in the tumors of the NDI high group, including two tumor suppressor genes, LRIG1 (p=1.99 x10-10) and WWOX (p=6.47 x 10-9). These methylation changes translated to an inverse relationship between gene expression for these tumor suppressor genes and NDI. We also identified significantly lower neutrophils in the NDI high tumors compared to NDI low tumors (p=0.001, 95% CI -0.112, -0.028). Conclusions: Overall, our analysis provides evidence that high neighborhood deprivation can lead to pro-tumorigenic changes in DNA methylation and gene expression that may impact the immune microenvironment, breast cancer progression, and overall survival.

Project description:Children's cognitive development and academic performance are linked to both fetal and early childhood factors, including preterm birth and family socioeconomic status. We evaluated whether the relationship between preterm birth (PTB) and first grade standardized test performance among Georgia public school students was modified by neighborhood deprivation in early childhood. The Georgia Birth to School cohort followed 327,698 children born in Georgia from 1998 to 2002 through to end-of-year first grade standardized tests. Binomial and log-binomial generalized estimating equations were used to estimate risk differences and risk ratios for the associations of both PTB and the Neighborhood Deprivation Index for the census tract in which each child's mother resided at the time of birth with test failure (versus passing). The presence of additive and multiplicative interaction was assessed. PTB was strongly associated with test failure, with increasing risk for earlier gestational ages. There was positive additive interaction between PTB and neighborhood deprivation. The main effect of PTB versus term birth increased risk of mathematics failure: 15.9% (95%CI: 13.3-18.5%) for early, 5.0% (95% CI: 4.1-5.9%) for moderate, and 1.3% (95%CI: 0.9-1.7%) for late preterm. Each 1 standard deviation increase in neighborhood deprivation was associated with 0.6% increased risk of mathematics failure. For children exposed to both PTB and higher neighborhood deprivation, test failure was 4.8%, 1.5%, and 0.8% greater than the sum of two main effects for early, moderate, and late PTB, respectively. Results were similar, but slightly attenuated, for reading and English/language arts. Our results suggest that PTB and neighborhood deprivation additively interact to produce greater risk among doubly exposed children than would be predicted from the sum of the effects of the two exposures. Understanding socioeconomic disparities in the effect of PTB on academic outcomes at school entry is important for targeting of early childhood interventions.

Project description:By the 3rd year of life, young children engage in a variety of prosocial behaviors, including helping others attain their goals (instrumental helping), responding to others' emotional needs (comforting), and sharing resources (costly giving). Recent work suggests that these behaviors emerge early, during the first 2 years of life (Svetlova et al., 2010; Thompson and Newton, 2012; Dunfield and Kuhlmeier, 2013). To date, however, work investigating early varieties of prosocial behavior has largely focused on Western samples and has not assessed the impact of poverty and inequality. In this work, we investigate prosocial behavior in 3-year-olds in Zambia, a lower-middle income country with high wealth inequality. Experiments were integrated into a larger public health study along with both objective and subjective (parent) measures of wealth and inequality. Three-hundred-seventy-seven children (Mean age = 36.77 months; SD = 2.26 months) were presented with an instrumental helping task, comforting task, and two steps of a giving task - one with higher cost (children could give away their only resource) and one with lower cost (children had three resources to give). As predicted, rates of prosociality varied hierarchically by the cost of the action: instrumental helping was the most common followed by comforting, lower cost giving, and higher cost giving. All prosocial behaviors were significantly correlated with one another (with the exception of high cost giving), and with general cognitive ability. Objective family wealth did not predict any of the child's prosocial behaviors. However, subjective beliefs showed that mothers who believed that they had more than others in their village had children who were more likely to engage in instrumental helping, and mothers who believed that village inequality was a problem had children who were more likely to engage in low cost giving. Low cost giving was also more likely for children whose parents reported reading storybooks to them. This suggests that costly giving in the context of pretend play may relate to children's experience with using stories as representations of real life events. The results suggest both cultural differences and universalities in the development of prosociality and point to environmental factors that influence prosociality.

Dataset Information

Neighborhood Deprivation Negatively Impacts Children's Prosocial Behavior.

Publications

Neighborhood Deprivation Negatively Impacts Children's Prosocial Behavior.

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