AA Women Research Articles

Estimated Daily Lactose Consumption in Healthy U.S. Adults in Relation to Lactase Persistence Genotype (rs4988235)

Abstract Objectives Lactase persistence (LP), a heritable trait in which lactose can be digested throughout adulthood, is often used to predict dairy intake. However, it is currently unknown how LP relates to daily lactose consumption in healthy US adults. The objective of the study was to estimate lactose from foods reported in the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) and to compare lactose and total dairy consumption in relation to LP genotypes. Methods ASA24 dietary data were collected from healthy Caucasians and Hispanics (n = 215) genotyped for the lactase persistence SNP ID: rs4988235. ASA24 outputs servings of dairy but not the nutrient lactose. Lactose was estimated by matching ASA24-reported foods to foods in the Nutrition Coordinating Center Food and Nutrient Database, which outputs lactose. Analysis of covariance was used to identify whether genotype influenced lactose and total dairy consumption with total energy intake and weight as covariates. Pairwise testing was conducted on the adjusted means using the Tukey adjustment to correct for multiple testing. Results Median lactose consumption for subjects with the AA genotype (homozygous LP) was 12.08 g (min: 0.91 g, max: 81.85 g), 10.05 g (min: 0.46 g, max: 45.82) for subjects with the AG genotype (heterozygous LP), and 8.97 g (min: 0.47, max: 38.96 g) for subjects with the GG genotype (homozygous lactase non-persistent). AA subjects consumed more lactose than GG subjects (P = 0.024). When stratifying by sex, there were no significant differences among genotypes in women, although GG women consumed the least amount of lactose compared to AA and AG women. AA men consumed more lactose than AG (P = 0.028) and GG men (P = 0.032). Subjects with the AA genotype consumed the most, and GG subjects the least amount of dairy. However, there were no significant differences in total dairy consumption among genotypes. Conclusions The median amount of lactose consumed daily by healthy adults is 9–12 g/day, with higher consumption by those with an LP genotype. Total dairy intake was not significantly influenced by genotype, highlighting the value in specifically estimating lactose consumption. Maximal lactose intake by lactase non-persisters exceeding 15 g/day suggests alternate routes of lactose catabolism. Funding Sources The California Dairy Research Foundation and the USDA-ARS.

County poverty levels influence genome-wide DNA methylation profiles in African American and European American women.

Our pilot study examined global DNA methylation and telomere length (TL) using DNA from saliva samples provided by 39 participants in the Arkansas Rural Community Health (ARCH) Study. TL was quantified by qPCR, and DNA methylation and DNA methylation age was assessed using the Illumina 850K Epic BeadChip. Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways that were DM between residents of counties with high or low poverty rates and by race [African American descent (AA) versus European American (EA) descent]. Among AA women, hypermethylation was more common in AA residents of counties with low compared to high poverty rates (70% vs. 30%). The top canonical pathways impacted by differential methylation were related to glucocorticoid receptor, p53, and estrogen-dependent breast cancer signaling in AA women. EA women living in low-poverty counties exhibited less hypermethylation of CpGs than those living in high-poverty counties (27% vs. 73%). The top canonical pathways were related to hereditary breast cancer, glucocorticoid receptor, androgen and PI3K/AKT signaling. Several genes involved in telomere maintenance were shown to be DM by county poverty levels. Therefore, the finding of this pilot study suggests county poverty levels may impact DNA methylation patterns in breast cancer-related pathways as well as genes involved in telomere maintenance. Larger studies should confirm our findings.

Abstract P1-09-15: DNA methylation markers influenced by BMI are associated with breast cancer

Abstract Body mass index (BMI) is a well-established risk factor for breast cancer. However, the underlying molecular mechanism through which BMI acts on breast cancer remain largely unknown. DNA methylation plays a critical role in regulating gene expression. Aberrant DNA methylation has been implicated in breast cancer development. We hypothesize that BMI influences DNA methylation that in turn leads to breast cancer. We therefore conducted a molecular epidemiological study to identify DNA methylation markers that are associated with BMI in healthy women and further determine the association of these DNA methylation changes with breast cancer development and occurrence. We analyzed 270 normal breast tissue from healthy women and 109 tumor tissue from breast cancer patients for genome-wide DNA methylation profiling using the Illumina Truseq® Methyl Capture EPIC sequencing technology. After data quality control, approximately 3 million CpG sites (sequencing depth≥10) were retained and included in further statistical analysis. Linear regression was performed to examine the association between BMI and each of CpG sites, adjusting for age and race. Bonferroni correction was used for control for multiple comparisons. We further investigated whether these BMI-associated DNA methylation markers were differentially methylated in normal and breast tissue. We found that 30 CpG sites were significantly associated with BMI (P< 1.5x 10-8) in normal breast tissue. Many of these GpG sites were also differentially methylated in tumor and normal breast tissue. Top CpG hits are near novel and putative cancer genes mainly involved in lipid metabolism and related reproductive phenotypes that increase breast cancer risk, including KIAA0232, SHZ2, LACTB, PAPPA, and DLGAP2. The most significant CpG site associated with BMI is on chr. 4 in KIAA0232 gene. Little is known about the function of this gene, but genetic variant near the gene are associated with platelet count and volume in GWAS. The second most significant hit is on chr.20 in gene TSHZ2. This gene is found downregulated in breast and prostate cancer. LACTB gene is a tumor suppressor that modulates lipid metabolism and cell state. Its mechanism of action involves alteration of mitochondrial lipid metabolism and differentiation of breast cancer cells. PAPPA gene plays a role in inflammation and promote invasion of cancer cells. DLGAP2 is an imprinted gene, and SNPs near DLGAP2 are associated with age at menarche in AA women. Our results suggest DNA methylation may intermediate the observed association between BMI and breast cancer. Further research is warranted to validate these findings in larger studies as well as to understand the regulatory network by linking data with gene expression. Citation Format: He C, Lin N, Castle J, Liu J, Liu Y, Wang C. DNA methylation markers influenced by BMI are associated with 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 P1-09-15.

ANXA2 expression in African American triple-negative breast cancer patients

Our aim was to determine the role of Annexin A2 (AnxA2), which we have previously found to contribute to the aggressiveness of TNBC, with AA TNBC patients and clinical outcome. We analyzed TCGA breast cancer database (n = 1098) to observe AnxA2 expression within breast cancer subtypes and is correlation with overall survival. Further, we examined breast tissue specimens (n = 119) through chromogenic in situ hybridization (CISH) and specimen were scored independently by two pathologists in a blinded study. In our TCGA analysis, high expression of AnxA2 was correlated with poor survival in patients with TNBC. AnxA2 gene expression was not correlated with poor survival in other breast cancer subtypes. AnxA2 average CISH intensity score (CISH score = 0, null expression to 3, high expression) for TNBC was significantly higher in comparison to estrogen receptor and/or progesterone receptor positive, human epidermal growth factor positive, and non-malignant tissues. Furthermore, AnxA2 average score was significantly higher in AA TNBC patients (CISH average score = 2.45 ± 0.3266) in comparison to Caucasian TNBC patients (CISH average score = 1.1 ± 0.4069). AnxA2 is overexpressed in TNBC, implicating AnxA2 as a contributor to the aggressive biology of TNBC in AA women.

Association of the oxytocin receptor gene with attitudinal trust: role of amygdala volume.

Previous studies have shown that genetic variations in rs53576, a common variant of the oxytocin receptor gene (OXTR) resulting from a single nucleotide polymorphism involving an adenine (A)/guanine (G) transition, are associated with attitudinal trust in men. However, the pathway from gene to behaviour has not been elucidated. We conducted the present study to determine whether amygdala volume mediates the association between OXTR rs53576 genotypes and attitudinal trust. Our results revealed that the left amygdala volume was significantly smaller in GG men than in AA and AG men, whereas it was significantly smaller in AA and AG women than in GG women. In addition, the left amygdala volume was negatively associated with attitudinal trust in men, whereas there was no such association in women. We also found a significant mediation effect of the left amygdala volume on the association between OXTR rs53576 genotypes and attitudinal trust in men. The results of our study suggest that the left amygdala volume plays a pivotal role in the association between OXTR rs53576 genotypes and attitudinal trust in men.

Bone Mineral Content/Density And Muscle Strength In Young Women From Different Racial/Ethnic Backgrounds - A Pilot Study

Race/ethnicity is a major factor influencing both bone mass and muscle mass (bone free lean mass - BFLM) since muscular forces can enhance bone strength by applying mechanical stress to the skeleton. PURPOSE: To examine group mean differences and the relationships between bone mineral content (BMC) and density (BMD) to BFLM and muscle strength in young women from different racial/ethnic backgrounds. METHODS: Twenty-seven young women aged 18-30 years self-identified themselves as Caucasian (Cau; n=6), South-Asian (SA; n=6), East-Asian (EA; n=4), Hispanic (His; n=6), and African-American (AA; n=5). Body composition (fat, BFLM, and BMC) and total and regional BMD were measured using Dual Energy X-Ray Absorptiometry, while jump test, leg press, and bilateral isokinetic strength testing of knee flexors/extensors were used to quantify lower limb muscle strength and power. International Physical Activity Questionnaire (IPAQ) classified women into low, moderate or high levels of physical activity. Ethnic differences in each outcome variable were determined using one-way ANOVA, while Pearson correlation coefficients quantified relationships between variables. Statistical significance was set at p < 0.05. RESULTS: Based on the entire sample (n=27), both total body BMD and BMC had significant positive relationships with total BFLM (r=0.78 and 0.87 respectively). Based on ethnicity, AA women had significantly higher total body and hip (left and right) BMC than His. Although non-significant, total BFLM values were highest for AA and lowest for EA and SA (47.7±9.6 kg vs. 37.9±5.5 kg and 37.8±5.5 kg respectively; p=0.08). Analysis of the entire sample revealed a significant positive relationship between MET minutes/week and total BFLM (r=0.45). As per IPAQ scores, highly active women had significantly lower percent body fat compared to moderately active women (26% ± 6% vs. 38% ± 7%; p=0.001). Finally, average muscular power (watts; W) during flexion at 60 deg/sec was significantly higher for Cau compared to EA and SA (54.98±18.74 W vs. 30.76±7.6 W and 27.7±9.0 W respectively; p=0.01). CONCLUSION: These findings suggest that BMC and BMD are significantly related to total BFLM, and that BMC varies across the ethnic groups, however, further data collection and analyses will validate the current findings.

Sistas Inspiring Sistas Through Activity and Support (SISTAS): Study Design and Demographics of Participants.

Recruiting racial, ethnic, and other underserved minorities into conventional clinic-based and other trials is known to be challenging. The Sistas Inspiring Sistas Through Activity and Support (SISTAS) Program was a one-year randomized controlled trial (RCT) to promote physical activity and healthy eating among AA women in SC to reduce inflammatory biomarkers, which are linked to increased breast cancer (BrCa) risk and mortality. This study describes the development, recruitment, and implementation of the SISTAS clinical trial and provides baseline characteristics of the study participants. SISTAS was developed using community-based participatory research (CBPR) approaches. At baseline, study participants completed assessments and underwent clinical measurements and blood draws to measure C-reactive protein (CRP) and interleukin-6 (IL-6). Participants randomized to the intervention received 12 weekly classes followed by nine monthly booster sessions. Post-intervention measurements were assessed at 12-week and 12-month follow-ups. We recruited a total of 337 women who tended to: be middle-aged (mean age 48.2 years); have some college education; be employed full-time; have Medicare as their primary insurance; be non-smokers; and perceive their personal health as good. On average, the women were pre-hypertensive at baseline (mean systolic blood pressure = 133.9 mm Hg; mean diastolic blood pressure = 84.0 mm Hg) and morbidly obese (mean BMI >40.0 kg/m2); the mean fat mass and fat-free mass among participants were 106.4 lb and 121.0 lb, respectively. The SISTAS RCT addresses some of the gaps in the literature with respect to CBPR interventions targeting AA women, such as implementing diet and physical activity in CBPR-based studies to decrease BrCa risk.

Propensity for excess gestational weight gain in African‐American women may be explained by hypometabolic factors in early pregnancy

BackgroundWomen with obesity are at increased risk for excess gestational weight gain. Studies in non‐pregnant women suggest that the etiology of weight gain may be different between African‐American and White women and this may cause higher retention of weight postpartum and the increased prevalence of obesity in offspring.ObjectiveTo conduct a cross‐sectional study in African‐American and White pregnant women to identify metabolic and behavioral risk factors for aberrant weight gain trajectories.DesignMetabolic and behavioral phenotyping was conducted in 66 pregnant women with obesity, expecting a single fetus, between 14 and 16 weeks of gestation. Energy expenditure was measured in free‐living conditions over 7 days using stable isotopes and during sleep in a room calorimeter. Body composition was measured by air displacement plethysmography and physical activity by SenseWear™ accelerometers. Fasting blood was collected to measure markers of metabolic health.ResultsAfrican‐American (AA, n=34) and White women (W, n=32) were comparable in age (27.7±0.6 years) but had a lower socio‐economic status and higher parity. The two groups were matched for BMI (36.9±0.7 kg/m2) and while body fat was not different (55.1±0.6%), AA women had more fat‐free mass (AA: 56.9±1.6 vs W: 51.6±1.1 kg, p=0.009) and tended to be more insulin resistant (HOMA‐IR, AA: 4.0±0.4 vs W: 3.1±0.3, p=0.06). Total daily energy intake was significantly lower in AA women compared to their white counterparts (AA: 2633±88 vs W: 2901±76 kcal/d, p=0.03), while diet composition and absolute total daily energy expenditure (TDEE) were not different between the two ethnic groups (AA: 2590±77 vs W: 2711±56 kcal/d, p=0.21). However, after correction for individual differences in body composition, TDEE was significantly lower in AA women (−231±74kcal/d, p=0.003). Similarly, energy expenditure during sleep was comparable between ethnicities in absolute terms (p=0.77), but lower in AA women after adjustment for body composition (−81±37kcal/d, p=0.03). Physical activity was not significantly different between AA and white women as assessed by calorimetrically data or by accelerometry (eg. time spent in activity, average intensity of activity (METs), or as #steps). We observed no differences in substrate oxidation (12h and sleeping RQ) or metabolic profile (plasma T3 and T4 concentrations, urinary epinephrine and norepinephrine excretion).ConclusionsEarly in pregnancy, African‐American and White women with obesity have similar energy intake and physical activity but energy expenditure per kg of metabolic mass is significantly lower in women who are African‐American. Energy requirements used by clinicians to counsel pregnant women on healthy weight gain are not race‐specific. The lower energy expenditure in African‐American women may therefore lead to unintentional overeating and contribute to the increasing prevalence of excessive gestational weight gain in African‐American women.Support or Funding InformationThis study was funded by the National Institutes of Health (R01DK099175; Redman) and in part by U54GM104940 and P30DK072476.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract P3-05-11: Immune and basal signature correlation to targeted therapies and race in QNBC patients

Abstract Background: African American women have worse prognosis and poor survival rates due to lack of Androgen Receptor expression. These subtypes, the Quadruple Negative Breast Cancers (QNBC), currently have no treatments. Previously, we found that AA TNBC have 28% more chance of being QNBC and have 25% higher rate of progression vs the Caucasian Americans (CA). Also, these QNBC patients have a unique immune and basal signature. Here, we explore individual genes and their correlation to race and immune therapies. Methods: We analyzed AR mRNA expression in 925 tumors from CA or AA women from The Cancer Genome Atlas and independently validated AR protein levels by immunohistochemistry in 197 primary tumors. Samples were dichotomized as AR positive or negative using mean gene expression cutoff. Gene expression comparisons among groups were determined using standard t-tests, ANOVA, and odds ratios with a significance threshold alpha of 0.05. a of 0.05. Therapy targets were selected from the list of significantly differentiated genes. Boxplots and heatmaps were made using R packages. Cumulative Incidence plots for time to progression were constructed using XLStats and Grays test for significance. Results: QNBC CA have higher expression of PDCD4 (p &amp;lt;.001), CD46 (p &amp;lt;.001), CD3EAP (p =.04) and CD84 (p =.07) compared to QNBC AA. CD47 (p = .63) and PD1 (p =.96) express no significant differences in race[CY1]. QNBC AA show higher expression of NFKB (p &amp;lt;.001), CCL2 (p &amp;lt;.001), and IL12 (p &amp;lt;.001) compared to QNBC CAs. Interestingly, QNBCs with high expressions of CD47 (p = .04) have poor prognosis[L2]. Thus, QNBC patients with low expression of CD46 (p =.025), PDCD4 (p &amp;lt; .001), and CD3EAP (p &amp;lt; .001) have poor prognosis and overall survival. Conclusions: Current immune targeted therapies like CD47 and PD1 looks favorable for treatment in some QNBC patients. Race appears to effect other major therapy target gene expressions in the QNBC immune basal signature as well. This may imply that QNBC AA and CA have different immune response which may explain racial progression differences. Assessment of immune markers may contribute to more accurate prognosis. Citation Format: Hughley RW, Colomb WD, Shweta T, Yates C. Immune and basal signature correlation to targeted therapies and race in QNBC patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-11.

Abstract 4998: Breast tumor FOXA1 protein expression and reproductive characteristics among African-American and European-American women

Abstract Background: Forkhead box protein A1 (FOXA1) plays a key role in determining estrogen receptor (ER) function and mammary ductal development and may repress the basal cell phenotype during differentiation of breast epithelium. While reproductive factors are known to influence breast cancer risk depending on the subtypes, data on the association of tumor FOXA1 protein expression and reproductive characteristics are very limited. Methods: Tissue microarrays comprising surgical tumors from 638 women (466 African-American [AA] and 172 European-American [EA], aged 20-75 years) with primary breast cancer in the Women’s Circle of Health Study (WCHS) were analyzed for FOXA1 expression by immunohistochemistry and automated image analysis. In-person interviews were conducted to obtain data on demographics, medical and family histories, and reproductive and menstrual histories. Logistic regression was performed for FOXA1 positivity (&amp;gt;10% cells with strong staining) with menopausal status, age at menarche, age at first live birth, parity, and breastfeeding, adjusting for age at diagnosis, family history of breast cancer, and history of benign breast disease. Results: FOXA1 expression was higher in tumors from EA compared to those from AA women (80% vs. 70% positivity, P=0.011). FOXA1 expression was highly correlated with ER positivity (88% positive in ER+ and 26% in ER- breast cancer among AA women; 90% and 29% respectively among EA women; both P&amp;lt;0.001). Among AA women, a higher number of live births was associated with lower FOXA1 expression (odds ratio [OR]=0.45, 95% confidence interval [CI]=0.22-0.91 for 2 live births and OR=0.44, 95% CI=0.20-0.91 for ≥3 live births, versus nulliparous). However, the inverse association was not observed among EA women, potentially due to the small sample size. Conclusion: In AA women, a higher number of live births, which has been related to greater risk of ER- breast cancer, is associated with lower FOXA1 expression. Because FOXA1 promotes luminal and represses the basal differentiation, respectively, the effects of parity on expression of FOXA1 may be the link whereby it increases risk of ER- breast cancer. (Funding: NIH P01CA151135, R01CA100598, R01CA185623, P30CA072720, K07CA201334; US Army Medical Research and Material Command DAMD-17-01-1-0334; the Breast Cancer Research Foundation; and the Philip L. Hubbell family) Citation Format: Ting-Yuan David Cheng, Rochelle Payne Ondracek, Song Yao, Wiam Bshara, Thaer Khoury, Gary R. Zirpoli, Warren Davis, Elisa V. Bandera, Michael Higgins, Christine B. Ambrosone. Breast tumor FOXA1 protein expression and reproductive characteristics among African-American and European-American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4998. doi:10.1158/1538-7445.AM2017-4998

Symptoms, cancer-related distress, and overall distress may contribute to racial disparities in the outcomes of patients with early-stage breast cancer.

Key Points Only 60% of AA women with early‐stage BC received at least 85% of the prescribed adjuvant chemotherapy within the prescribed timeframe. The number of symptoms and symptom distress were related to the ability to receive timely, full‐dose adjuvant chemotherapy. These findings provide an actionable area in which to potentially decrease cancer treatment disparities.

Abstract 12743: Risk of Cardiovascular Readmission Within 3 Years Following a Hypertensive Complication of Pregnancy

Introduction: Women with pregnancies complicated by pregnancy-induced hypertension (PIH) have increased cardiovascular (CV) risk decades later. We sought to determine if these women demonstrate greater CV risk more immediately. Methods: Using administrative data, we extracted all hospital-based deliveries in the state of Florida from 2004 through 2013. Deliveries and clinical diagnoses were determined using ICD-9 CM codes. Readmissions to any Florida hospital were identified using unique patient identifiers. Our primary predictor was PIH, defined as a composite of gestational hypertension, pre-eclampsia, and eclampsia. Outcomes of interest were CV readmission, defined as a composite of myocardial infarction, stroke, or heart failure; non-CV readmission, and no readmission within 3 years of index delivery. Clinical profiles and maternal outcomes were stratified by readmission status. The association between risk of readmission and PIH was determined using logistic regression. Results: A total of 1,834,166 records from delivering mothers were included (mean age 27.3 ± 6.2 years; 53% white, 25% African American [AA], 20% Hispanic). There were 4,732 CV readmissions and 321,713 non-CV readmissions within 3 years of index delivery. When stratified by readmission status, there was a higher make-up of women with PIH in the CV readmission group compared with the other groups (16.5% CV readmission, 9.3% non-CV readmission, 7.4% no readmission; p&lt;0.001) and a higher rate of obesity (13% CV readmission, 5% non-CV readmission, 3% no readmission; p&lt;0.001). Sixty percent of women in the CV readmission group were AA. Women with PIH had a higher multivariate risk of both CV readmission (OR 1.71; 95% CI 1.48 - 1.86) and non-CV readmission (OR 1.08; 95% CI 1.07 - 1.10). Compared with white women, AA women had the highest risk for CV readmission (OR 3.39; 95% CI 3.17 - 3.63) and Hispanic women had the lowest risk of CV readmission (OR 0.60; 95% CI 0.53 - 0.67) after adjustment for PIH. Conclusion: In this diverse sample, women with PIH have a higher risk of CV readmission within 3 years of delivery. Significant racial and ethnic differences were seen in the risk for CV readmission among women with pregnancies complicated by PIH with a markedly higher risk in AA women.

Alternative Locales for the Health Promotion of African American Men: A Survey of African American Men in Chicago Barbershops.

African American men (AA) carry unequal burdens of several conditions including cancer, diabetes, hypertension, and HIV. Engagement of diverse populations including AA men in research and health promotion practice is vital to examining the health disparities that continue to plague many racially and ethnically diverse communities. To date, there is little research on best practices that indicate locations, community areas and settings to engage AA men in research and health promotion. Traditionally, the AA church has been a key area to engage AA men and women. However, changing tides in attendance of AA parishioners require additional information to identify areas where AAs, particularly, AA men congregate. The AA barbershop has been identified as a place of social cohesion, cultural immersion and solidarity for AA men but specific sub-populations of AA men may be underrepresented. To further investigate additional locales where AA men congregate, this study engaged AA barbers and clients in several urban community barbershops in Chicago, Illinois. 127 AA men over age 18y/o receiving grooming services in 25 Chicago area barbershops across 14 predominantly AA communities were consented and recruited for a quantitative survey study. The self-administered surveys were completed in ~15min and $10 compensation was provided to men. Descriptive statistics were reported for demographic variables and for frequency of responses for locations to find AA men of specific age ranges for health promotion and screening activities. Outside of the traditionally used churches or barbershops, the top recommended recruitment sites by age were: 18-29y/o- city park or a recreational center; 30-39y/o- gym, bars or the street; 40-49y/o- various stores, especially home improvement stores, and the mall; and 50y/o+- fast food restaurants in the mornings, such as McDonalds, and individual's homes. The study participants also reported that locations where AA men congregate vary by age. Findings from this study illustrate that AA barbers and barbershops remain a key stakeholder in health promotion among AA men. The findings also demonstrate the need for additional research to examine best practices for identifying locations where diverse groups of AA men that vary by age and sexual orientation may congregate in order to support increased health promotion among AA men.

Genetic variations in the Hippo signaling pathway and breast cancer risk in African American women in the AMBER Consortium.

The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. Dysfunction of the Hippo pathway components has been linked with breast cancer stem cell regulation, as well as breast tumor progression and metastasis. TAZ, a key component of the Hippo pathway, is highly expressed in triple negative breast cancer; however, the associations of genetic variations in this important pathway with breast cancer risk remain largely unexplored. Here, we analyzed 8309 germline variants in 15 genes from the Hippo pathway with a total of 3663 cases and 4687 controls from the African American Breast Cancer Epidemiology and Risk Consortium. Odds ratios (ORs) were estimated using logistic regression for overall breast cancer, by estrogen receptor (ER) status (1983 ER positive and 1098 ER negative), and for case-only analyses by ER status. The Hippo signaling pathway was significantly associated with ER-negative breast cancer (pathway level P = 0.02). Gene-based analyses revealed that CDH1 was responsible for the pathway association (P < 0.01), with rs4783673 in CDH1 statistically significant after gene-level adjustment for multiple comparisons (P = 9.2×10(-5), corrected P = 0.02). rs142697907 in PTPN14 was associated with ER-positive breast cancer and rs2456773 in CDK1 with ER-negativity in case-only analysis after gene-level correction for multiple comparisons (corrected P < 0.05). In conclusion, common genetic variations in the Hippo signaling pathway may contribute to both ER-negative and ER+ breast cancer risk in AA women.

Influence of Activity Before or During Pregnancy on Fetal and Infant Heart Outcomes

We hypothesized that exercise during pregnancy will have greater influence than exercise prior to pregnancy on improved offspring heart rate; this was tested by measuring fetal and infant heart rate. Women were classified into 4 groups: AA=active before and during pregnancy, AI=active before, inactive during pregnancy, IA= inactive before, active during pregnancy, and II= inactive before, inactive during pregnancy. Based on current guidelines, active was defined as ≥150min per week of moderate intensity exercise. Those not meeting criteria were classified as inactive. Fetal (36 wk) and infant (1 mo) heart rates were acquired via ECG and MCG recordings. Data from 83 uncomplicated pregnancies (AA=39, AI=13, IA=12, II=19) was analyzed. We found that fetuses from AA women had lowest heart rates of all groups, especially compared to fetuses of II women (p=0.002). In infant HR, we found significantly lower HR in infants exposed to exercise in utero relative to those not exposed with greatest differences in HR between AA and II groups (p=0.001). As we anticipated, we have found significantly lower fetal and infant heart rates in exercise‐exposed offspring regardless of women's activity prior to pregnancy. However, this dataset does not control for fetal/infant activity state, which may influence findings. These results further support the benefit of exercise as the primary mechanism for positive affects on fetal and infant heart rate. These data further support a prenatal programming effect on the fetal cardiac autonomic nervous system from maternal physiological events during gestation.Support or Funding InformationEast Carolina University StartUp funds

Abstract IA30: Insights into metabolome of breast cancer

Abstract Metabolomics describes the science of quantifying the levels of metabolites (e.g., small molecules &amp;lt;1kDa) that are the byproducts of cellular metabolism. Unlike genomics, transcriptomics and proteomics, metabolomic analysis involves reduced complexity because of fewer endpoints and allows the assay of composite downstream outputs from complex interconnected cellular processes. These aspects both facilitate bioinformatic analysis and may accentuate subtle upstream gene/protein level alterations. Comparisons of metabolomic profiles from tissues or bodily fluids from one diseased state to another permits the identification of pathways and processes that may drive the phenotype in question. Our recent profiling of 200 metabolites using mass spectrometry in benign and malignant breast tissues from ancestry-verified AA and EA women, revealed altered levels of specific metabolites (or associated pathways) in AA TN BCa compared to EA TN tumors. Key among them was elevated levels of 2- hydroxyglutaric acid (2-HG), a mitochondrial onco-metabolite that was elevated in a subset of predominantly AA TN BCa with poor clinical outcome. Tumors with high 2-HG had a distinct methylation signature exhibiting activation of the MYC oncogene and were associated with elevated levels of fatty acids and lipids. Taken together, we expect these studies help understand the disparity in the clinical behavior of TN BCa. Further, we expect biochemical profiles to be useful in stratifying tumors for various pathway-based treatment regimens. Citation Format: Arun Sreekumar. Insights into metabolome of breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr IA30.

Abstract IA42: Risk factors and ovarian cancer in African American women: Contributors to disparities

Abstract IA42: Risk factors and ovarian cancer in African American women: Contributors to disparities

Genetic Variations in Magnesium-Related Ion Channels May Affect Diabetes Risk among African American and Hispanic American Women1–3

Prospective studies consistently link low magnesium intake to higher type 2 diabetes (T2D) risk. We examined the association of common genetic variants [single nucleotide polymorphisms (SNPs)] in genes related to magnesium homeostasis with T2D risk and potential interactions with magnesium intake. Using the Women's Health Initiative-SNP Health Association Resource (WHI-SHARe) study, we identified 17 magnesium-related ion channel genes (583 SNPs) and examined their associations with T2D risk in 7287 African-American (AA; n = 1949 T2D cases) and 3285 Hispanic-American (HA; n = 611 T2D cases) postmenopausal women. We performed both single- and multiple-locus haplotype analyses. Among AA women, carriers of each additional copy of SNP rs6584273 in cyclin mediator 1 (CNNM1) had 16% lower T2D risk [OR: 0.84; false discovery rate (FDR)-adjusted P = 0.02]. Among HA women, several variants were significantly associated with T2D risk, including rs10861279 in solute carrier family 41 (anion exchanger), member 2 (SLC41A2) (OR: 0.54; FDR-adjusted P = 0.04), rs7174119 in nonimprinted in Prader-Willi/Angelman syndrome 1 (NIPA1) (OR: 1.27; FDR-adjusted P = 0.04), and 2 SNPs in mitochondrial RNA splicing 2 (MRS2) (rs7738943: OR = 1.55, FDR-adjusted P = 0.01; rs1056285: OR = 1.48, FDR-adjusted P = 0.02). Even with the most conservative Bonferroni adjustment, two 2-SNP-haplotypes in SLC41A2 and MRS2 region were significantly associated with T2D risk (rs12582312-rs10861279: P = 0.0006; rs1056285-rs7738943: P = 0.002). Among women with magnesium intake in the lowest 30% (AA: ≤0.164 g/d; HA: ≤0.185 g/d), 4 SNP signals were strengthened [rs11590362 in claudin 19 (CLDN19), rs823154 in SLC41A1, rs5929706 and rs5930817 in membra; HA: ≥0.313 g/d), rs6584273 in CNNM1 (OR: 0.71; FDR-adjusted P = 0.04) and rs1800467 in potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) (OR: 2.50; FDR-adjusted P = 0.01) were significantly associated with T2D risk. Our findings suggest important associations between genetic variations in magnesium-related ion channel genes and T2D risk in AA and HA women that vary by amount of magnesium intake.

Strategies to influence attitudes towards pharmacotherapies for alcohol and opioid use disorders

Clinical Trials Network 0019 (CTN 0019) (Tross et al., 2008). The CTN 0019 protocol was a multi-site randomized clinical trial that assessed the intervention of Safer Sex Skills Building (SSSB) in women substance abusers on reducing HIV sexual risk. The current study consists of 124 AA women from the CTN 0019 dataset. Participation eligibility required women to be at least 18 years of age, proficient in English, enrolled in substance abuse treatment, and to acknowledge unprotected heterosexual intercourse within the past 6 months. Results: In the current sample, 70.2% (N=87) endorsed lifetime physical abuse from a male sexual partner. Of the women experiencing physical abuse, 33.3% (N=29) reported physical abuse from their current main partner. Independent sample t-tests showed that women who self-reported physical abuse had lower levels of SRP than those who did not (t(118) =3.18; p< .01). The moderation model of SRP decreasing the relationship between victimization and risky sexual behavior approached significance (p= .064). Conclusions: The current study is among the first to examine moderating factors of SRP in substance-abusing African American women. The findings from this study provide evidence that substance abuse interventions may benefit from activities promoting the development of sexual relationship power and self-efficacy in substance-abusing African American women who have experienced victimization. Financial support: No financial support was provided for the current study.

Abstract 4983: IRAK4 and breast cancer cell migration in culture and zebrafish xenografts

Abstract Growing evidence indicates that incongruities in the inflammatory and immune response pathways contribute to tumorigenesis. We seek to explore the underlying biological mechanisms that both promote and inhibit breast cancer (BrCa) tumorigenesis via innate immune pathways involving the Toll-like receptors (TLRs) and their associated agonists. Women of African descent (AA) are an understudied group at high risk for developing aggressive BrCa. Therefore, we previously examined the occurrence of single nucleotide polymorphisms (SNPs) in selected genes along TLR pathways among a small cohort of AA women with breast cancer and identified a SNP in the central regulatory kinase IRAK4 that was associated with increased breast cancer risk. In silico predictions suggest that the IRAK4 minor variant rs4251545 codes for an Ala428Thr missense mutation that introduces a potential phosphorylation site in the extreme carboxy terminus (XCT) of the IRAK-4 kinase domain. The current study tests the hypothesis that functional IRAK4 promotes BrCa cell growth and migration using in vitro (cultured human BrCa cell) and in vivo (zebrafish BrCa xenograft) models. Materials and methods: ER-positive MCF7 and triple-negative MDA-MB-231 (wild-type IRAK4) and MDA-MB-468 (IRAK4 w/rs4251545) human BrCa cell lines were compared. Cultured cells were treated for 24 hours with or without IRAK1/4 inhibitor. Cell migration and cell growth among BrCa lines were compared using wound healing and crystal violet assays, respectively. BrCa cell xenografts of zebrafish (ZF) embryos were examined for metastatic potential and the physiologic effects of morpholino inhibition of ZF IRAK4 among embryos with and without BrCa xenograft burdens were compared. In addition, zebrafish/tumor xenograft model was used to address the in vivo metastatic property of BrCa cells and the effect of targeting zebrafish irak4 using morpholino (MO) knockdown approach in the tumor-host environment on the metastatic behavior of MDA-MB-468 cells. Results: Treatment with IRAK1/4 inhibitor delayed BrCa migration and growth in all BrCa cells lines. Relative in vivo migration rates/ (or metastatic property) of MDA-MB-231 and MDA-MB-468 BrCa xenografts in ZF resemble in vitro rates, in which MDA-MB-231s migrate metastasized more rapidly/ (or aggressively). MO inhibition of ZF zebrafish IRAK4 irak4 gene expression in the host environment MDA-MB-468 xenografted fish inhibits MDA-MB-468 metastasis in the zebrafish/tumor xenograft. Conclusion: Inhibition of IRAK4 reduces BrCa growth and migration in vitro and in vivo in zebrafish. The development of drugs that target IRAK4 and other regulators of the innate immune pathway may help modulate BrCa tumor progression. Citation Format: K. Sean Kimbro, Karine Ferri-Lagneau, Jamil Haider, Susan Yeyeodu, Xiaohe Yang, TinChung Leung. IRAK4 and breast cancer cell migration in culture and zebrafish xenografts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4983. doi:10.1158/1538-7445.AM2014-4983