Cohort Of African American Women Research Articles

Does stress from incarceration of family and friends contribute to signs of early vascular ageing in African American women?

BackgroundEarly vascular ageing (EVA) contributes to elevated risk of cardiovascular disease (CVD), which disproportionately affects African American women. Incarceration, an event disproportionately impacting African Americans, may be a stressor contributing...

Combined oral contraceptive utilization and uterine fibroid incidence: A prospective study in a cohort of African-American women.

Published associations between combined oral contraceptive use and uterine fibroid development have lacked prospective imaging with ultrasound to distinguish between incident and prevalent fibroids. The Study of Environment, Lifestyle, and Fibroids prospectively followed fibroid-free, African-American women (the group with the highest disease burden in the U.S.) to identify incident cases. We examined associations between combined oral contraceptive use and the 40-month cumulative risk of fibroids. History of hormonal contraceptive use was collected via telephone interview at enrollment. Fibroid identification was performed using transvaginal ultrasonography at enrollment, and at 20 and 40-months of follow-up. Inverse probability weights for exposures and censoring were used to construct weighted risk ratios (wRR) and weighted risk different (wRD) estimators which control for differences in fibroid risk factors between exposure groups. In addition, unweighted fully adjusted log-binomial regression models (aRR) were run for comparison. Of the 1,308 participants in the analysis sample, 70% had used combined oral contraceptives and 17% developed fibroids by 40 months. We observed an inverse association between ever use of combined oral contraceptives and cumulative fibroid incidence (wRR: 0.78; 95% Confidence Interval (CI): 0.60, 1.00; wRD: -0.05, 95% CI: -0.11, 0; aRR: 0.76, 95% CI: 0.60, 0.98). Fibroid incidence was greater in participants who started using combined oral contraceptives after age 17 years than among younger initiators, though the restriction to ever-users made this estimate less precise (wRR: 1.25; 95% CI: 0.89, 1.76; wRD: 0.04, 95% CI: -0.02, 0.10). No consistent patterns of fibroid incidence were seen among ever-users for duration of, or years since, last combined oral contraceptives use.

Perceived childhood neighborhood safety and sleep health during childhood and adulthood among a cohort of African American women

ObjectiveTo investigate associations between perceived childhood neighborhood safety and sleep over the life course. MethodsAmong a cohort of 1693 Black/African American women aged 23–35 years at enrollment (2010–2012), participants recalled neighborhood safety (safe vs. unsafe) when they were 5, 10, and 15 years old. Participants’ mothers/caregivers and participants reported sleep-related health behaviors at age 5. We used ordinal logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for sleep-related health behaviors (i.e., rarely/never or sometimes vs. mostly/always going to bed by 8:00 p.m., bed in a quiet room, bed in a dimly lit or unlit room), separately. Adulthood sleep duration and insomnia symptoms were reported at enrollment and over three follow-up periods. We applied generalized estimating equations to log binomial regression models to estimate relative risks (RR) for adulthood sleep characteristics. Results and conclusionsFour percent of participants reported an unsafe neighborhood at age 5 years, only, and 12% reported an unsafe neighborhood at all ages. Participants in perceived unsafe vs. safe neighborhoods at age 5 had higher odds of poor sleep-related health behaviors (e.g., rarely/never or sometimes going to bed in a quiet room: OR = 1.73 [1.27–2.35]). Participants in perceived unsafe vs. safe neighborhoods throughout childhood had higher risk of short sleep (RR = 1.10 [1.02–1.18]) and insomnia symptoms (RR = 1.07 [1.00–1.15]) during adulthood after adjustment for life course socioeconomic characteristics and adulthood health behaviors and characteristics. Perceived unsafe childhood neighborhood was associated with poorer sleep over the life course and may serve as an early intervention target.

Association between serum 25-hydroxyvitamin D and antimüllerian hormone levels in a cohort of African-American women

ObjectiveTo examine the association between serum 25-hydroxyvitamin D [25(OH)D] and ovarian reserve as measured by antimüllerian hormone (AMH). DesignCross-sectional study. SettingDetroit, Michigan area. SubjectsData were obtained from a prospective cohort of self-identified Black/African-American women aged 23-35 years at the time of enrollment (N=1593), had no prior diagnosis of polycystic ovary syndrome (PCOS), were not currently pregnant, and were not missing AMH or 25(OH)D measures. ExposureSerum 25(OH)D. Main outcome measureSerum AMH was the main outcome. Linear regression was used to examine the associations between categorical 25(OH)D (<12 ng/mL, 12-<20, 20-<30, ≥30) and continuous natural log-transformed AMH. Associations between 25(OH)D and high (upper 10th percentile: >7.8 ng/mL) or low AMH (<0.7 ng/mL) were estimated with logistic regression. Models were adjusted for age, age-squared, BMI, hormonal contraceptive use, smoking, and exercise. ResultsThe 25(OH)D levels were low; 70% of participants were below 20 ng/mL. In fully-adjusted models, compared to 25(OH)D levels <12 ng/mL, those with 25(OH)D levels of 12-<20, 20-<30 and ≥30 ng/mL had an AMH level that was 7% (95% CI: -4, 20) , 7% (95% CI: -6, 22), or 11% higher (95% CI: -7, 34), respectively. Moreover, these groups had a lower odds of having low AMH (OR[95% CI): 0.63 (0.40, 0.99), 0.60 (0.34, 1.07), 0.76 (0.35, 1.65), respectively, and the highest category of 25(OH)D had a higher odds of having high AMH, (OR [95% CI]: 1.42 [0.74, 2.72]). Exclusion of participants with either irregular cycles or very high AMH (>25 ng/mL), did not alter the associations. ConclusionTaken together, these results indicate that higher levels of 25(OH)D are associated with a slightly higher AMH, a lower odds of low AMH, and a higher odds of high AMH. This evidence is weak, however, since only a small percentage of participants had high 25(OH)D. Future studies should examine populations with a wide distribution of 25(OH)D levels (both high and low), with a clinical trial design, or with longitudinal measures of both 25(OH)D and AMH.

Characterization of Vaginal Microbial Community Dynamics in the Pathogenesis of Incident Bacterial Vaginosis, a Pilot Study.

Despite more than 60 years of research, the etiology of bacterial vaginosis (BV) remains controversial. In this pilot study, we used shotgun metagenomic sequencing to characterize vaginal microbial community changes before the development of incident BV (iBV). A cohort of African American women with a baseline healthy vaginal microbiome (no Amsel criteria, Nugent score 0-3 with no Gardnerella vaginalis morphotypes) were followed for 90 days with daily self-collected vaginal specimens for iBV (≥2 consecutive days of a Nugent score of 7-10). Shotgun metagenomic sequencing was performed on select vaginal specimens from 4 women, every other day for 12 days before iBV diagnosis. Sequencing data were analyzed through Kraken2 and bioBakery 3 workflows, and specimens were classified into community state types. Quantitative polymerase chain reaction was performed to compare the correlation of read counts with bacterial abundance. Common BV-associated bacteria such as G. vaginalis , Prevotella bivia , and Fannyhessea vaginae were increasingly identified in the participants before iBV. Linear modeling indicated significant increases in G. vaginalis and F . vaginae relative abundance before iBV, whereas the relative abundance of Lactobacillus species declined over time. The Lactobacillus species decline correlated with the presence of Lactobacillus phages. We observed enrichment in bacterial adhesion factor genes on days before iBV. There were also significant correlations between bacterial read counts and abundances measured by quantitative polymerase chain reaction. This pilot study characterizes vaginal community dynamics before iBV and identifies key bacterial taxa and mechanisms potentially involved in the pathogenesis of iBV.

Cyclin A2 and Ki-67 proliferation markers could be used to identify tumors with poor prognosis in African American women with breast cancer.

Diagnosed invasive breast carcinomas in African American patients are more aggressive compared with those in Caucasian patients and diagnosed at later stages of the disease with higher grade tumors. Despite advances in breast cancer systemic treatment, new prognostic and predictive biomarkers are still needed. Therefore, potential biomarkers were chosen to correlate with different subtypes, recurrence, and survival of invasive breast cancer in a cohort of African American women. Eight protein biomarkers (ER, PR, HER2, Cyclin A2, Cytokeratin 5, Vimentin, Bcl2, and Ki-67) were evaluated using tissue microarrays (TMAs) and immunohistochemistry (IHC). The IHC results from TMAs were analyzed by both supervised and unsupervised clustering methods. The predictive clusters for the supervised and unsupervised methods were compared for agreement with the empirical classification. Kappa values were used to determine the overall percent correct clusters and agreement between specific clusters. Chi-square statistics was used to examine the association between hierarchical and multinomial logistic clustering methods. Five subtypes of breast tumors with distinct protein expression patterns were identified among the studied 166 breast tumors. Luminal B tumors have been distinguished from luminal A tumors by staining for cell cycle proteins Cyclin A2 and Ki-67, which promote cell proliferation. Forty-nine percent were stained positive for Cyclin A2, 39.2% positive for Ki-67, and 37% positive for both Cyclin A2 and Ki-67. The age of patients did not show any significant effect whether five (p-value= 0.576) or eight (p-value= 0.605) biomarkers were used, which indicating that age did not have any influence on the classification of the subtypes. Ninety percent of the thirty triple negative tumors were positive for Cyclin A2 or Ki-67 or both. Six-year overall survival was better for luminal A tumors (76%) than luminal B tumors (71%). Likewise, six-year relapse-free survival was better for luminal A tumors (76%) than luminal B tumors (29%). Discovery of molecular markers such as Cyclin A2 and Ki-67, and subtypes that are most prevalent in African Americans could lead to a better understanding of the factors contributing to higher morbidity and mortality in this group and to aid in decision-making to offer earlier treatment.

Abstract 13094: Extracellular Vesicles Associate With Cardio-Metabolic Status and Endothelial Dysfunction in a Cohort of African-American Women

Extracellular vesicles (EVs) are emerging as promising biomarkers for cardiovascular disease (CVD) and contributors to CVD pathogenesis. Plasma EVs access the endothelium from various vascular beds allowing them to impact endothelial function and inform on the global particulate secretome produced by parenchymal, vascular and immune cells. In this study we examined associations between plasma EVs and biochemical and physiological parameters in a cohort of African American (AA) women at risk for CVD. We also examined EV effect on coronary endothelial function. This study will serve as baseline data for a longitudinal study aimed to determine the effects of exercise on EVs and endothelial function in a similar cohort.A cohort of 24 AA women between 22-71 yrs, with BMI between 26-47 kg/m 2 and ASCVD risk scores between 2.3-22.1 were included in the study. EVs were isolated from fasted heparinized plasma using size exclusion chromatography. EV size and numbers were determined using nanoparticle tracking analysis. Lipids, inflammatory cytokines, and metabolic panels were measured at the time of blood draw. Human coronary endothelial cells were treated with EVs from participants and endothelial barrier function and migration were measured using ECIS technology. Associations were determined using multivariable linear regression analysis, adjusted for BMI and ASCVD risk.We found a negative association (beta=-0.712, p&lt;0.01) between total triglycerides (TG), TG rich lipoprotein (Lp), and EV size; EV concentration was positively associated (beta= 0.51-0.61, p&lt;0.01) with TG rich Lp, LDL cholesterol and TNFa. Reduced endothelial barrier function due to EVs was positively associated with monocyte counts (beta=0.42, p&lt;0.05). EVs effect on increased endothelial migration was strongly and negatively associated with monocyte counts (beta=-0.85, p&lt;0.001), IL8 and CXCl10 (beta=-0.56-0.46, p&lt;0.05).Collectively these data show that EVs number and size strongly associate with circulating lipids, while EV impact on endothelial dysfunction is associated with inflammatory markers. EVs are therefore promising indicators of endothelial dysfunction that associate with inflammatory and metabolic markers even after adjusting for BMI and ASCVD risk.

Abstract MP05: The Impact Of Neighborhood Social Environment On Natural Killer Cells In A Community-based Cohort Of African American Women

Introduction: Chronic exposure to environmental stressors is associated with racial and ethnic disparities in cardiovascular disease (CVD) risk factors. African American (AA) women are at highest risk for obesity and subsequent CVD development. Obesity as a CVD risk factor and psychosocial stressors have been associated with altered Natural Killer (NK) cell distribution and function. Less is known about how perceived and objective neighborhood social environment relates to NK cell distribution and function. Hypothesis: More favorable neighborhood social environment would associate with a greater number and more functional NK cell population. Methods: We recruited 40 AA women from a Washington, DC community-based cohort and determined the NK cell profile using flow cytometry according to their CD3/CD56 expression on the cell surface. Neighborhood social environment was measured by neighborhood environment (NE) perceptions and objective neighborhood deprivation index (NDI). NE perceptions were measured using validated questionnaires to calculate overall NE perceptions, perceived neighborhood violence, physical/social environment, social cohesion, and safety (higher score=more favorable perceptions). NDI was measured using U.S. Census data on census-tract level features (i.e., housing characteristics, education, income, poverty) where higher NDI=lower NE socioeconomic level. Multivariable regression models were used to determine associations between neighborhood social environment and NK cell number. Additionally, regression models were adjusted for Atherosclerotic Cardiovascular Disease (ASCVD) risk and BMI, unless otherwise specified. Results: Among this community-based cohort of AA women (N=40 mean age 58.8 ±12.0; BMI 34.2 ±6.9), overall NE perceptions were associated with overall NK cell numbers before and after adjustments for ASCVD and BMI (β=0.48, p=0.007, β=0.50, p=0.004). Perceived lack of violence was associated with increased NK cell number (β=0.38, p=0.04) even after the adjustment for ASCVD and BMI (β=0.39, p=0.03). Similar trends were observed with social cohesion and NK cells (β=0.32, p=0.06) and with perceived favorable physical/social environment and NK cells (β=0.34, p=0.07). In contrast, we found that safety did not show any significant association with NK cell numbers (β=0.28, p=0.13). Finally, NDI as an objective measure of neighborhood SES did not associate with NK cell numbers (β=-0.05, p=0.74). Conclusion: Together, our data suggest that perceived neighborhood social environment associates with NK cell numbers, while objective measures do not. These findings suggest that changes in NK cell populations may be driven by perceived social environment factors and could alter CV risk. Future studies are needed to determine the potential impact of social environment stressors on NK cell subtypes, receptor expression, and function.

Predicted Vitamin D Status and Colorectal Cancer Incidence in the Black Women's Health Study.

Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations. We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of participants. We calculated cumulative average predicted vitamin D score at every cycle by averaging scores from cycles up to and including that cycle. Using Cox proportional hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer incidence according to predicted score quartiles. Over follow-up, 488 incident colorectal cancers occurred. Compared with women in the highest quartile of predicted vitamin D score, those in the lowest had an estimated 41% (HR = 1.41; 95% CI, 1.05-1.90) higher colorectal cancer risk. Comparable HRs were 1.44 (95% CI, 1.02-2.01) for colon and 1.34 (95% CI, 0.70-2.56) for rectal cancer. Low vitamin D status may lead to elevated colorectal cancer risk in African American women. Our findings, taken together with established evidence that vitamin D levels are generally lower in African Americans than other U.S. groups, suggest that low vitamin D status may contribute to the disproportionately high colorectal cancer incidence among African Americans.

Evaluating Experiences of Stress and Coping Among African American Women During the COVID-19 Pandemic to Inform Future Interventions.

African American (AA) women experience disproportionate levels of chronic disease, which is theorized to be driven by greater exposure to acute and chronic stress. The coronavirus (COVID-19) pandemic has further exacerbated existing health disparities among AA communities. Understanding how AA women have experienced and responded to stress during the pandemic may help to inform how future interventions can better address physical and mental well-being in AA communities. Drawing from stress and coping models and an ecological framework, the present study conducted a theory-based qualitative assessment of stress-related experiences during the pandemic among a cohort of AA women, including (1) sources of stress, (2) coping strategies, (3) perceptions of health-related behaviors, (4) the role of community, and (5) recommendations for future interventions. After completing a group-based physical activity intervention program during the COVID-19 pandemic, a cohort of AA women (N =17, Mage= 49.3 ± 11.24) completed individual interviews. Sessions were conducted by phone, audiotaped, transcribed, and coded by independent raters (rs = .71-.73). Themes were identified using deductive and inductive approaches. Among sources of stress directly related to the pandemic, being at home, getting sick, and homeschooling/parenting were the most frequently discussed themes. Participants engaged in active coping (problem and emotion-focused), with health behaviors, social support, and religion/spirituality, emerging as frequently discussed themes. Although some participants reported passive coping strategies (e.g., avoidance), this approach was less pronounced. These qualitative results are used to guide suggestions for future interventions that jointly address stress and health-related behaviors in order to improve translation of research into practice and policy for future pandemics and disasters.

Associations of single and multiple per- and polyfluoroalkyl substance (PFAS) exposure with vitamin D biomarkers in African American women during pregnancy

Vitamin D has been linked to various physiological functions in pregnant women and their fetuses. Previous studies have suggested that some per- and polyfluoroalkyl substances (PFAS) may alter serum vitamin D concentrations. However, no study has investigated the relationship between PFAS and vitamin D in pregnant women. This study aims to evaluate the associations of serum PFAS with serum total and free 25-hydroxyvitamin D (25(OH)D) during pregnancy in a cohort of African American women in Atlanta, GA. Blood samples from 442 participants were collected in early pregnancy (8-14 weeks of gestation) for PFAS and 25(OH)D measurements, and additional samples were collected in late pregnancy (24-30 weeks) for the second 25(OH)D measurements. We fit multivariable linear regressions and weighted quantile sum (WQS) regressions to estimate the associations of individual PFAS and their mixtures with 25(OH)D concentrations. We found mostly positive associations of total 25(OH)D with PFHxS (perfluorohexane sulfonic acid), PFOS (perfluorooctane sulfonic acid), PFDA (perfluorodecanoic acid), and NMeFOSAA (N-methyl perfluorooctane sulfonamido acetic acid), and negative associations with PFPeA (perfluoropentanoic acid). For free 25(OH)D, positive associations were observed with PFHxS, PFOS, PFOA (perfluorooctanoic acid), and PFDA, and a negative association with PFPeA among the women with male fetuses in the models using 25(OH)D measured in late pregnancy. In mixture models, a quartile increase in WQS index was associated with 2.88ng/mL (95%CI 1.14-4.59) and 5.68ng/mL (95%CI 3.31-8.04) increases in total 25(OH)D measured in the early and late pregnancy, respectively. NMeFOSAA, PFDA, and PFOS contributed the most to the overall effects among the eight PFAS. No association was found between free 25(OH)D and the PFAS mixture. These results suggest that PFAS may affect vitamin D biomarker concentrations in pregnant African American women, and some of the associations were modified by fetal sex.

A Prospective Analysis of Red and Processed Meat Intake in Relation to Colorectal Cancer Incidence in the Black Women’s Health Study

Abstract Objectives African Americans have the highest incidence of colorectal cancer (CRC) of any racial/ethnic group in the US. High intake of red and processed meats has been shown to increase CRC risk in populations of European ancestry, but evidence in African American populations is limited. The association between saturated and monounsaturated fatty acid intakes, the primary types of fat in red and processed meat, and CRC is inconclusive. Thus, we prospectively assessed the intake of red and processed meats and dietary saturated and monounsaturated fatty acids in relation to CRC risk, utilizing the Black Women's Health Study (BWHS, 1995–2018). Methods Dietary data were derived from validated food frequency questionnaires completed in 1995 and 2001 by 52,695 BWHS participants. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression adjusted for energy, fiber, and discretionary fat. Results Over a median follow-up of 22 years, 564 women developed incident CRC. Total red meat intake was associated with a 25% increased risk of CRC per 100 g/day (HR = 1.25; 95% CI: 0.94–1.66), which was primarily due to intake of unprocessed red meat (HR = 1.33, 95% CI: 1.05–1.70). Processed meat and total saturated and monounsaturated fatty acid intakes were not associated with an increased risk of CRC. Conclusions Unprocessed red meat intake was associated with an increased risk of CRC in this cohort of African American women. The strong evidence, now including African American women, that red meat plays a role in the etiology of CRC suggests opportunities for prevention. Funding Sources This research was funded by National Institutes of Health grants U01 CA164974 and R01 CA058420, the Karin Grunebaum Cancer Research Foundation, and the Boston University Peter Paul Career Development Professorship.

Vaginal Microbiome Composition in Early Pregnancy and Risk of Spontaneous Preterm and Early Term Birth Among African American Women.

ObjectiveTo evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women.MethodsVaginal samples collected in early pregnancy (8-14 weeks’ gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231).ResultsNearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (L. iners dominated) and just 16% had CST I, II, or V (non-iners Lactobacillus dominated). Compared to vaginal CST I, II, or V (non-iners Lactobacillus dominated), both CST III (L. iners dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of Gardnerella vaginalis (p=0.011), non-iners Lactobacillus (p=0.016), and Mobiluncus curtisii (p=0.035) and the presence of Atopobium vaginae (p=0.049), BVAB2 (p=0.024), Dialister microaerophilis (p=0.011), and Prevotella amnii (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%.ConclusionsIn this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB.

Abstract PO-197: Neighborhood- and individual-level psychosocial stress and risk of breast cancer among Black women

Abstract Background Psychosocial stress has been linked to adverse health outcomes, including cancer. However, prior studies have not consistently demonstrated an association between psychosocial stress and risk of breast cancer. Further investigation is needed to help elucidate the relation, especially among Black women, who experience some unique stressors. Methods Within the Black Women’s Health Study, an ongoing prospective cohort of 59,000 African American women, we analyzed the association between neighborhood- and individual-level psychosocial stress factors and risk of breast cancer by estrogen receptor (ER) status. Participants reported individual-level factors on baseline and follow-up questionnaires. Neighborhood-level factors were determined by linking participant addresses to year 2000 and 2010 United States Census data, including median household income, percentage of adults aged ≥25 years who have completed college, percentage unemployed, and percentage of individuals below the poverty line. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for established breast cancer risk factors. Results During follow-up from 1995 to 2017, 2,167 incident breast cancer cases (1,259 ER+; 687 ER-) were identified. In multivariable models, women living in the most disadvantaged neighborhoods had a 26% (HR=1.26, 95% CI 1.00-1.58 for highest vs. lowest quartile) higher risk of ER- breast cancer compared to those living in the least disadvantaged neighborhoods. The comparable HR for lowest versus highest quartile of neighborhood socioeconomic status (SES) was 1.24 (95% CI 0.98-1.57). Conversely, living in the lowest quartile of neighborhood SES was associated with a reduced risk of ER+ breast cancer (HR=0.83, 95% CI 0.70-0.98). With respect to individual-level factors, marital status (married/living together vs. single: HR=1.29, 95% CI 1.08-1.53), education (≥16 vs. ≤12 years of education: HR=1.18, 95% CI 1.00-1.41), and childhood sexual abuse (sexual assault ≥4 times vs. no abuse: HR=1.35, 95% CI 1.01- 1.79) were associated with higher risk of ER+, but not ER- breast cancer. Women who experienced racism more frequently in their daily lives had a modestly elevated risk of ER+ (highest vs. lowest quartile of racism score: HR=1.14, 95% CI 0.94-1.38), but not ER- breast cancer. Conclusion In this cohort of African American women, neighborhood disadvantage and lower neighborhood SES were associated with an increased risk of ER- breast cancer, whereas individual stressors were associated with an increased risk of ER+ breast cancer. Neighborhood-level factors are proxies for social and environmental exposures that could influence breast cancer risk through direct (e.g., chronic stress, inflammation) and indirect (e.g., barriers to healthy behaviors) pathways. Because residence in low SES neighborhoods is common among Black women, these exposures could contribute to observed racial disparities in incidence of ER- breast cancer. Citation Format: Lauren E. Barber, Gary R. Zirpoli, Yvette C. Cozier, Kimberly A. Bertrand, Lucile L. Adams-Campbell, Julie R. Palmer. Neighborhood- and individual-level psychosocial stress and risk of breast cancer among Black women [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-197.

Health Beliefs and Breast Cancer Screening Practices Among African American Women in California.

African American women continue to have higher mortality rates of breast cancer when compared to other women, and evidence suggests that early detection of breast cancer can lead to favorable outcomes, yet there remains a paucity of literature about health beliefs and the utilization of three screening practices, namely breast self-examination, clinical breast examination and mammography in California, a state that currently has one of the highest breast cancer mortality rates among African American women. To investigate the relationship between health beliefs and three breast cancer detection practices, e.g. breast self-examination, clinical breast examination, and mammography in a cohort of African American women. Using a descriptive correlational design, a convenience sample of two hundred and eighty-two (n = 282) self-identified women from six regional chapters of a national Black women's political organization in California, completed a Demographic Data Questionnaire and Champion's Health Belief Model Scale which assessed the hypothesized relationships of health beliefs and breast cancer detection practices. Among this culturally diverse group of women (49.8% American, 28.8% African, 21.4% West Indian), health motivation was positively related to the practice of BSE and annual physician visitation for clinical breast examinations. Health locus of control was positively related to the practice of BSE. Having relatives and friends who were diagnosed with breast cancer was strongly associated with having a mammogram and annual physician visitation for clinical breast examinations. These findings may be used to target and develop interventions that are tailored to the unique characteristics of these diverse women.

4292 Epigenetic Age and Depressive Symptoms in African American Women with Cardiometabolic Conditions

OBJECTIVES/GOALS: To examine the relationship between epigenetic age acceleration (EAA) and depressive symptoms in a cohort of African American women (AAW) with cardiometabolic conditions (CMC) including hypertension, diabetes, obesity; and to explore clinical phenotypes of depressive symptoms in this population. METHODS/STUDY POPULATION: This secondary analysis utilized genomic and longitudinal clinical data from AAW in the InterGEN cohort (n = 250). EWAS data was used to estimate EAA based on the Horvath method, which incorporates the DNA methylation statuses at 353 specific CpG sites and regresses this epigenetic age on chronological age to determine EAA. Pearson’s correlations and linear regression will be used to examine the relationship between EAA and depressive symptoms and a linear mixed model will investigate this relationship over four time points during a two-year period. Clinical phenotyping of depressive symptoms will be explored using a cluster analysis. RESULTS/ANTICIPATED RESULTS: Analysis is underway and will be complete by the time of presentation. We hypothesize that higher EAA will associate with higher depressive symptoms and poorer trajectories over time. We expect that this relationship may be meditated by the presence of CMCs. Exploratory analysis of clinical phenotyping is expected to provide descriptive evidence with respect to specific depressive symptoms or clusters which are most associated with EAA and CMCs. These results will address several gaps. To our knowledge, this is the first study to examine the relationship of EAA and depressive symptoms considering the role of CMC, in a historically understudied population with disproportionate risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Depression limits life quality and quantity and is highly comorbid in CMC. AAW have high risk of comorbidity, and this study furthers knowledge of depression and aging with a clinically accessible marker and aids recognition of a heterogenous phenotype in an undertreated population.

Abstract P5-11-12: Longitudinal changes in volumetric breast density and fibroglandular volume with endocrine therapy in African American women with estrogen receptor positive breast cancer

Abstract Background and Aim: Reduction in breast density has been proposed as a biomarker of response to endocrine therapy (ET). The vast majority of current data are derived from white or Asian women. Because baseline breast density is associated with race, it is possible that changes in breast density with treatment may also be affected by race. Our objective was to assess the impact of ET on volumetric breast density (VBD) and fibroglandular volume (FGV) in African American (AA) women with invasive breast cancer. Methods: We conducted a retrospective study of AA women diagnosed with estrogen receptor positive invasive breast cancer at our institution from 2009-2013. Mammograms within two years prior to diagnosis and at least 6 months post-diagnosis were utilized for comparing density measurements. Using Volpara automated software, VBD and FGV were measured for the contralateral normal breast by averaging the respective values measured on the craniocaudal and mediolateral oblique views. Results: 51 women met the inclusion criteria and were confirmed to have received ET. Sixteen women received tamoxifen, 34 received an aromatase inhibitor, and medication data was unavailable in one case. The mean age at diagnosis was 56 years (range 29-72, median 55). 53% of women had stage I disease, 29% had stage II disease, and 18% had stage III disease. The majority of women had ER+ PR+ HER2 - disease (82.4%). 53.0% of women received systemic chemotherapy and all but one woman were treated surgically. Average body mass index (BMI) at diagnosis was 36.5, with data not available for 22 women. The mean time between diagnosis and baseline mammogram was 32 days, and the mean time between follow-up mammogram and baseline mammogram was 401 days. Average BMI at one year follow up was 33.7, with data not available for 19 women. The mean baseline VBD was 7.5% (range 1.9-21.5%, median 6.3%) and the mean follow-up VBD was 6.9% (range 2.0-23.6%, median 5.6%). Fifteen women had a longitudinal increase in VBD. The mean absolute change in VBD was -0.6% (range -3.4% to +9.8%, median 0.7%), with a mean 8.0 percent decrease from baseline to follow-up (range -0.7 to +0.5, median 0.1). The mean baseline FGV was 72.3 cm3 (range 18.5-208.4, median 65.3) and the mean follow-up FGV was 69.7 cm3 (range 22.7-197.5, median 60.5). Nineteen women had a longitudinal increase in FGV. The mean absolute reduction in FGV was 2.6 cm3 (range -53.3 to 49.3, median 4.8), with a mean 0.9 percent decrease from baseline to follow-up (range -111.6 to +53.0, median 5.2). Conclusions: We observed an overall decrease in Volpara-calculated VBD and FGV in our cohort of AA women treated with ET. It remains to be determined whether changes in VBD and FGV across serial mammograms may be a biomarker for response to ET in women of all races. Large prospective studies are needed to evaluate the effects of ET on longitudinal changes in VBD and FGV while controlling for confounders such as menopausal status, BMI, and chemotherapy. Citation Format: Johnson HM, Shivalingappa H, Wong JH, Muzaffar M, Verbanac K, Vohra NA. Longitudinal changes in volumetric breast density and fibroglandular volume with endocrine therapy in African American women with estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-11-12.

Abstract IA20: A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans

Abstract In addition to being frequently mutated in sporadic cancer, the p53 tumor suppressor also contains several coding region variants that alter function and can contribute to increased cancer risk. We previously published that the Pro47Ser variant of p53 exists in approximately 1-2% of individuals of African descent, and that this variation prevents a key phosphorylation event on p53, and reduces the ability of this protein to induce cell death (1). We recently published a mouse model for this variant, and show that this mouse develops a striking incidence of sporadic cancer, predominantly hepatocellular cancer but also including cancers of the pancreas, stomach, and intestine. In a cohort of African American women with breast cancer, we found evidence for an association of Pro47Ser with pre-menopausal cancer incidence (HR 1.7, p&amp;lt;0.025) (2). Mechanistically, we find that the Pro47Ser variant displays a very selective transcriptional defect compared to wild-type p53, for a subset of target genes involved in ferroptosis and metabolism (3). Metabolic studies on mouse and human cells, as well as our Pro47Ser mouse, indicate that there is a profound difference in metabolism, with cells and mice containing Pro47Ser showing a significant predilection for aerobic glycolysis instead of oxidative phosphorylation. Interestingly, this defect actually leads to an apparent increase in fitness in these mice. We recently conducted a drug screen to search for compounds that may be selectively efficacious in tumors containing the Pro47Ser variant; this analysis revealed several compounds with increased efficacy against Pro47Ser tumors, compared to identical tumors with wild-type p53 (4). Our combined data suggest that the Pro47Ser variant may underlie increased cancer risk in African Americans, and that we may be able to personalize therapy for individuals containing this variant. 1. Li X, Dumont P, Della Pietra A, Shetler C, Murphy ME. The codon 47 polymorphism in p53 is functionally significant. J Biol Chem 2005;280(25):24245-51. PubMed PMID: 15851479. 2. Murphy ME, Liu S, Yao S, et al. A functionally significant SNP in TP53 and breast cancer risk in African-American women. NPJ Breast Cancer 2017;3:5. PubMed Central PMCID: PMC5445618. 3. Jennis M, Kung CP, Basu S, et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 2016;30(8):918-30. PubMed Central PMCID: PMC4840298. 4. Basu S, Barnoud T, Kung CP, Reiss M, Murphy ME. The African-specific S47 polymorphism of p53 alters chemosensitivity. Cell Cycle 2016;15(19):2557-60. PubMed Central PMCID: PMC5053554. Citation Format: Maureen E. Murphy. A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA20.

Inflammatory signatures distinguish metabolic health in African American women with obesity.

Obesity-driven Type 2 diabetes (T2D) is a systemic inflammatory condition associated with cardiovascular disease. However, plasma cytokines and tissue inflammation that discriminate T2D risk in African American women with obese phenotypes are not well understood. We analyzed 64 circulating cytokines and chemokines in plasma of 120 African American women enrolled in the Black Women’s Health Study. We used regression analysis to identify cytokines and chemokines associated with obesity, co-morbid T2D and hypertension, and compared results to obese women without these co-morbidities, as well as to lean women without the co-morbidities. We then used hierarchical clustering to generate inflammation signatures by combining the effects of identified cytokines and chemokines and summarized the signatures using an inflammation score. The analyses revealed six distinct signatures of sixteen cytokines/chemokines (P = 0.05) that differed significantly by prevalence of T2D (P = 0.004), obesity (P = 0.0231) and overall inflammation score (P < E-12). Signatures were validated in two independent cohorts of African American women with obesity: thirty nine subjects with no metabolic complications or with T2D and hypertension; and thirteen breast reduction surgical patients. The signatures in the validation cohorts closely resembled the distributions in the discovery cohort. We find that blood-based cytokine profiles usefully associate inflammation with T2D risks in vulnerable subjects, and should be combined with metabolism and obesity counselling for personalized risk assessment.

Physical Activity and Risk of Preterm Birth in a Cohort of African American Women.

Few studies have identified modifiable risk factors that are associated with the prevention of preterm delivery (PTD). This study examined the relationship between PTD and physical activity during pregnancy. Data were obtained by medical record review and postpartum questionnaires from a cohort of African American women (N=1,410) delivering singleton infants. Physical activity was self-reported and analyses compared any and none. Additional analyses classified leisure time physical activity (LTPA) and walking for a purpose as 0, 1 to 19, 20 to 39, and 40minutes per day or more and stair climbing as 0, 1 to 5, 6 to 9, and 10 or more times per day. Log-Poisson models adjusted for previous PTD, pregnancy complications, and income were used to examine the association between PTD and physical activity during pregnancy across body mass index categories. Overall, 16.4% of deliveries were preterm. LTPA was associated with a decreased prevalence of PTD (prevalence ratio [PR], 0.73; 95% confidence interval [CI], 0.55-0.96), but stratification by maternal prepregnancy body mass index suggested that LTPA was only protective against PTD among women with normal weight (PR, 0.43; 95% CI, 0.23-0.79). Stair climbing 10 or more times per day was associated with a decreased prevalence of PTD among women with normal weight (PR, 0.32; 95% CI, 0.11-0.94) and women with overweight (PR, 0.24; 95% CI, 0.07-0.80) only. Walking for a purpose (e.g., to the store, the bus stop, or to work) was not associated with PTD. African American women who participate in either LTPA or stair climbing during pregnancy have a decreased prevalence of PTD, but the protective effect varied by maternal body mass index.