Low educational attainment is associated with excess cancer mortality. However, the mechanisms driving this association remain unknown. Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated the associations of participant and parental/caregiver education with cancer mortality using Cox proportional hazards models, adjusting for socio-demographic characteristics and health conditions. We used principal components analysis to generate indices of measures representing the social determinants of health (SDOH) and health behaviors. We used structural equation modeling to determine if the association between educational attainment and cancer mortality was mediated by these domains. Among 30,177 REGARDS participants included in this analysis, 3798 (12.6%) had less than a high school degree. In fully adjusted models, those without a high school education experienced about 50% greater risk of death than high school graduates and higher (White participants HR: 1.47; 95% CI: 1.23, 1.76 and Black HR: 1.54; 95% CI: 1.33, 1.79). There was evidence of a modest mediation effect for the association between education and cancer mortality by the SDOH domain score (White total effect HR: 1.25; 95% CI: 1.18, 1.33, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.21; 95% CI: 1.14, 1.28 and Black total effect HR: 1.24; 95% CI: 1.18, 1.29, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.19; 95% CI: 1.14, 1.24). There was no evidence of mediation by the health behaviors score. No significant associations were found for female caregiver/mother's or male caregiver/father's education (N = 13,209). In conclusion, participant education was strongly associated with cancer mortality, and this association was partially mediated by the SDOH domain score.

Metabolic syndrome (MetS) is characterized by a cluster of biological irregularities. The purpose of this analysis was to examine the association of MetS with BC among Nigerian women, and for the first time evaluate this association by molecular subtype. MetS was defined as having at least 3 out of 5 of: high blood pressure (≥ 130/85 mm Hg), reduced HDL (< 50 mg/dL), elevated triglyceride (> 150 mg/dL), high waist circumference (≥ 80 cm), and prior diagnosis of diabetes or elevated fasting glucose level (≥ 100 mg/dL). Among 296 newly diagnosed BC cases and 259 healthy controls, multivariable logistic regression models were utilized to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for the association between MetS and BC overall. Multinomial logistic regression models were used to evaluate each molecular subtype (Luminal A, Luminal B, HER2-enriched and triple-negative or TNBC). After adjusting for age, socio-demographic and reproductive risk factors, there was a positive association between MetS and BC (aOR: 1.84, 95% CI: 1.07, 3.16). In stratified analyses, MetS was associated with BC regardless of BMI status; however, the estimate was significant only among normal weight women (aOR: 3.85; 95% CI: 1.25, 11.90). MetS was significantly associated with TNBC subtype (aOR: 4.37, 95% CI: 1.67, 11.44); associations for other molecular subtypes were not statistically significant. MetS appears to be a robust risk factor for BC, particularly for TNBC. Public health and clinical interventions can provide substantial benefits in reducing the burden of MetS and preventing BC among Nigerian women.

Background: Nigeria reports the highest age-standardized mortality rate for breast cancer (BC) among African countries and disproportionately high rates of high-grade cancer. Histological grade is a strong predictor of mortality, and evidence suggests that educational attainment influences cancer outcomes. Objective: We characterize the association between educational trends across the life course and BC grade at diagnosis. \ Methods: Data on 224 BC patients enrolled in the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study was analyzed. Participant and parental (mother and father) education was categorized as low (primary school or less) or high (secondary school or greater). Accordingly, the educational trend across the life-course was determined for each participant relative to each parent: stable high, increasing, decreasing, or stable low. BC grade was classified as high (grade 3) or low (grades 1-2). Findings: About 34% of participants, 71% of fathers, and 85% of mothers had low education. Approximately one-third of participants were diagnosed with high-grade BC. Participants with low-grade BC were more likely to have highly educated fathers (p = 0.04). After adjusting for age, comorbidities, marital status and mammogram screening, participants with highly educated fathers were 60% less likely to have high-grade BC (aOR 0.41; 95% CI 0.20 to 0.84) compared to those with less-educated fathers. Stable high life-course education relative to father was also associated with a significantly lower likelihood of having high-grade BC (aOR 0.36; 95% CI 0.15 to 0.87) compared to stable low life-course education. No significant associations were observed for the participant's education, mother's education, or life-course education relative to mother. Conclusions: Early-life socioeconomic status (SES) may influence BC grade. This deserves further study to inform policies that may be useful in reducing high-grade BC in Nigeria.

Limited prospective data have examined the effects of adverse childhood experiences (ACEs) on outcomes as early as elementary school, and few studies have explored cortisol and oxytocin as biomarkers for risk and resilience that may predict later life outcomes. The Hair Biomarkers Study (HBS-I) evaluated healthy preschool children (age 9-72 months) using parent surveys and scalp hair to measure cortisol (HCC; ng/mg) and oxytocin concentrations (HOC; ng/mg) via ELISA. Prospective follow-up at elementary school (age 7-12 years) included school attendance, Child Behavior Checklist (CBCL), and health outcomes. The cohort (N = 189) was 62% male, 41% White, and 90% living in a nuclear family. In multivariate negative binomial, linear, and logistic regression models, 1+ versus 0 ACEs at preschool was associated with 57% higher absenteeism in first-grade (95% CI: 1.02, 2.41), 12.3 percentile higher CBCL Total Problems (95% CI: 1.69, 22.89), and 3.7-fold greater odds of medically unexplained symptom(s) (95% CI: 1.12, 12.04). Higher preschool HOC predicted fewer school absences (RR: 0.90; 95% CI: 0.82, 0.98), while higher HCC predicted more sleep problems (OR: 1.49; 95% CI: 1.02, 2.18). Higher parental stress at preschool age predicted internalizing (Est: 1.39; 95% CI: 0.82, 1.95) and externalizing problems (1.17; 95% CI: 0.67, 1.67), and lower child health ratings (OR: 0.92; 95% CI: 0.86, 0.97). Preschool ACEs exposure was consistently associated with poorer outcomes across all 3 domains of academics, behavioral problems, and health. Collaboration among pediatricians, schools, mental health professionals, and community organizations is essential to mitigate ACEs-related long-term sequelae.