Perceived Experiences of racism in Relation to Genome-Wide DNA Methylation and Epigenetic Aging in the Black Women's Health Study.

BACKGROUND: African American women have a disproportionate burden of disease compared to US non-Hispanic white women. Exposure to psychosocial stressors may contribute to these health disparities. Racial discrimination, a major stressor for African American women, could affect health through epigenetic mechanisms. METHODS: We conducted an epigenome-wide association study (EWAS) to examine the association of interpersonal racism (in daily life and in institutional settings) with DNA methylation in blood in 384 participants of the Black Women's Health Study (BWHS). We also evaluated whether a greater number of perceived experiences of racism was associated with epigenetic aging as measured using different methylation clocks. Models were adjusted for chronological age, body mass index, years of education, neighborhood SES, geographic region of residence, alcohol drinking, smoking, and technical covariates. RESULTS: Higher scores of racism in daily life were associated with higher methylation levels at the cg04494873 site in chromosome 5 (ß = 0.64%; 95% CI = 0.41%, 0.87%; P = 6.35E-08). We also replicated one CpG site, cg03317714, which was inversely associated with racial discrimination in a previous EWAS among African American women. In the BWHS, higher scores of racism in daily life were associated with lower methylation levels at that CpG site (ß = -0.94%; 95% CI = -1.37%, -0.51%; P = 2.2E-05). Higher racism scores were associated with accelerated epigenetic aging in more than one methylation clock. CONCLUSIONS: Exposure to discriminatory events may affect the epigenome and accelerate biological aging, which may explain in part the earlier onset of disease in African American women.

Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia.

BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16). CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.

Micro- and Macronutrient Intake in Elderly Costa Ricans: The Costa Rican Longevity and Healthy Aging Study (CRELES).

Costa Rica, a middle-income country in Central America, has a life expectancy similar or even higher than richer countries. This survival advantage is more evident among the elderly, who have one of the lowest mortality rates in the world. Dietary factors may play a role in this extended longevity. We have shown that a traditional rural diet is associated with longer leukocyte telomere length-a biomarker of aging-among elderly Costa Ricans. In the present study, we used data from the Costa Rican Longevity and Healthy Aging Study (CRELES) to characterize further rural and urban diets of the elderly (60+ years). A validated food frequency questionnaire was used to assess usual diet. We used energy-adjusted regression models to compare the intake of micro- and macronutrients between rural and urban regions of the country. Elderly rural residents had a higher consumption of carbohydrates (but lower glycemic index), fiber, dietary iron, and used more palm oil for cooking than elderly urban dwellers. On the other hand, elderly subjects living in urban areas had a higher intake of total fat, mono and polyunsaturated fat, alcohol and dietary calcium compared to elderly rural residents. Our results are similar to earlier reports of middle-aged Costa Ricans and add to the characterization of diet differences in rural and urban regions of the country.

DNA Methylation Is a Potential Biomarker for Cardiometabolic Health in Mexican Children and Adolescents.

DNA methylation (DNAm) is a plausible mechanism underlying cardiometabolic abnormalities, but evidence is limited among youth. This analysis included 410 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to two time points in late childhood/adolescence. At Time 1, DNAm was quantified in blood leukocytes at long interspersed nuclear elements (LINE-1), H19, and 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD-2), and at Time 2 in peroxisome proliferator-activated receptor alpha (PPAR-α). At each time point, cardiometabolic risk factors were assessed including lipid profiles, glucose, blood pressure, and anthropometry. Linear mixed effects models were used for LINE-1, H19, and 11ß-HSD-2 to account for the repeated-measure outcomes. Linear regression models were conducted for the cross-sectional association between PPAR-α with the outcomes. DNAm at LINE-1 was associated with log glucose at site 1 [ß = -0.029, p = 0.0006] and with log high-density lipoprotein cholesterol at site 3 [ß = 0.063, p = 0.0072]. 11ß-HSD-2 DNAm at site 4 was associated with log glucose (ß = -0.018, p = 0.0018). DNAm at LINE-1 and 11ß-HSD-2 was associated with few cardiometabolic risk factors among youth in a locus-specific manner. These findings underscore the potential for epigenetic biomarkers to increase our understanding of cardiometabolic risk earlier in life.

Sedentary patterns and cardiometabolic risk factors in Mexican children and adolescents: analysis of longitudinal data.

BACKGROUND: Sedentary behavior is a modifiable risk factor for cardiometabolic health; however, the assessment of total sedentary time may not capture youth's highly active and interrupted activity patterns. This study examined the associations between sedentary activity patterns and cardiometabolic risk factors among Mexican youth, who have a disproportionate burden of metabolic diseases, using a repeated measure design out of a longitudinal data. METHODS: 570 subjects in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, who were followed up to three-time points during adolescence, were included. Bout duration, and frequency and percentages of waking time spent in specific intensities of activity, were quantified using ActiGraph wGT3X-BT wrist accelerometers. Self-reported questionnaires were used to query the usual duration of different sedentary behaviors. Outcomes were fasting lipid profile, markers for glucose homeostasis, anthropometry, and blood pressure. Associations were modeled using linear mixed-effects models, and isotemporal substitution approach was additionally used to assess the effect of replacing objectively assessed sedentary activity with other activity intensities, adjusting for potential confounders. RESULTS: Each hour of self-reported screen-based time was positively associated with diastolic blood pressure (mm Hg) [ß = 0.30, 95% confidence interval (95% CI) = 0.10, 0.51], and an hour of other sedentary time was associated with log serum glucose (mg/dL) [ß = 0.01, 95% CI = 0.004, 0.017]. Substitution models showed that replacing 5% of sedentary time with moderate to vigorous physical activity (MVPA) was associated with lower waist circumference (cm) [ß = - 1.35, 95% CI = - 1.91, - 0.79] and log serum triglycerides (mg/dL) [ß = - 0.11, 95% CI = - 0.18, - 0.03]. Substituting one uninterrupted sedentary bout with light activity was associated with lower insulin (µIU/mL) [ß = - 0.06, 95% CI = - 0.10, - 0.02]. CONCLUSIONS: Sedentary time was associated with cardiometabolic risk factors in Mexican youth in a context-specific manner. Replacing sedentary time with higher intensities was associated with improvements in some cardiometabolic markers.

Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk.

BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

Multivariate, region-based genetic analyses of facets of reproductive aging in White and Black women.

BACKGROUND: Age at final menstrual period (FMP) and the accompanying hormone trajectories across the menopause transition do not occur in isolation, but likely share molecular pathways. Understanding the genetics underlying the endocrinology of the menopause transition may be enhanced by jointly analyzing multiple interrelated traits. METHODS: In a sample of 347 White and 164 Black women from the Study of Women's Health Across the Nation (SWAN), we investigated pleiotropic effects of 54 candidate genetic regions of interest (ROI) on 5 menopausal traits (age at FMP and premenopausal and postmenopausal levels of follicle stimulation hormone and estradiol) using multivariate kernel regression (Multi-SKAT). A backward elimination procedure was used to identify which subset of traits were most strongly associated with a specific ROI. RESULTS: In White women, the 20 kb ROI around rs10734411 was significantly associated with the multivariate distribution of age at FMP, premenopausal estradiol, and postmenopausal estradiol (omnibus p-value = .00004). This association did not replicate in the smaller sample of Black women. CONCLUSION: This study using a region-based, multiple-trait approach suggests a shared genetic basis among multiple facets of reproductive aging.

Admixture mapping of anthropometric traits in the Black Women's Health Study: evidence of a shared African ancestry component with birth weight and type 2 diabetes.

Prevalence of obesity, type 2 diabetes (T2D), and being born with low birth weight are much higher in African American women compared to U.S. white women. Genetic factors may contribute to the excess risk of these conditions. We conducted admixture mapping of body mass index (BMI) at age 18, adult BMI, and adult waist circumference and waist-to-hip ratio adjusted for BMI using 2918 ancestral informative markers in 2596 participants of the Black Women's Health Study. We also searched for evidence of shared African genetic ancestry components among the four examined anthropometric traits and among birth weight and T2D. We found that global percent African ancestry was associated with higher adult BMI. We also found that African ancestry at 9q34 was associated with lower BMI at age 18. Our shared ancestry analysis identified ten genomic regions with local African ancestry associated with multiple traits. Seven out of these ten genomic loci were related to T2D risk. Of special interest is the 12q14-21 region where local African ancestry was associated with low birth weight, low BMI, high BMI-adjusted waist-to-hip ratio, and high T2D risk. Findings in the 12q14-21 genomic locus are consistent with the fetal insulin hypothesis that postulates that low birth weight and T2D have a common genetic basis, and they support the hypothesis of a shared African genetic ancestry component linking low birth weight and T2D in African Americans. Future studies should identify the actual genetic variants responsible for the clustering of these conditions in African Americans.

The oral microbiome in relation to pancreatic cancer risk in African Americans.

BACKGROUND: African Americans have the highest pancreatic cancer incidence of any racial/ethnic group in the United States. The oral microbiome was associated with pancreatic cancer risk in a recent study, but no such studies have been conducted in African Americans. Poor oral health, which can be a cause or effect of microbial populations, was associated with an increased risk of pancreatic cancer in a single study of African Americans. METHODS: We prospectively investigated the oral microbiome in relation to pancreatic cancer risk among 122 African-American pancreatic cancer cases and 354 controls. DNA was extracted from oral wash samples for metagenomic shotgun sequencing. Alpha and beta diversity of the microbial profiles were calculated. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between microbes and pancreatic cancer risk. RESULTS: No associations were observed with alpha or beta diversity, and no individual microbial taxa were differentially abundant between cases and control, after accounting for multiple comparisons. Among never smokers, there were elevated ORs for known oral pathogens: Porphyromonas gingivalis (OR = 1.69, 95% CI: 0.80-3.56), Prevotella intermedia (OR = 1.40, 95% CI: 0.69-2.85), and Tannerella forsythia (OR = 1.36, 95% CI: 0.66-2.77). CONCLUSIONS: Previously reported associations between oral taxa and pancreatic cancer were not present in this African-American population overall.

Diet and Leukocyte Telomere Length in a Population with Extended Longevity: The Costa Rican Longevity and Healthy Aging Study (CRELES).

Elderly Costa Ricans have lower mortality rates compared to their counterparts from developed countries. Reasons for this survival advantage are not completely known. In the present study, we aimed to identify dietary factors associated with leukocyte telomere length (LTL), a marker of biologic aging, in the elderly population of Costa Rica. We conducted prospective analysis in 909 participants aged 60+ years from the Costa Rican Longevity and Healthy Aging Study (CRELES). We used a food frequency questionnaire to assess usual diet. We calculated dietary patterns using Principal Component Analysis (PCA). We used generalized linear models to examine the association of dietary patterns and food groups with leukocyte telomere length. We found two major dietary patterns explaining 9.15% and 7.18% of the total variation of food intake, respectively. The first dietary pattern, which represents a traditional Costa Rican rice and beans pattern, was more frequent in rural parts of the country and was positively associated with baseline LTL: ß (95% CI) = 42.0 base-pairs (bp) (9.9 bp, 74.1 bp) per one-unit increase of the traditional dietary pattern. In analysis of individual food groups, intake of grains was positively associated with baseline LTL: ß (95% CI) = 43.6 bp (13.9 bp, 73.3 bp) per one-serving/day increase of consumption of grains. Our results suggest that dietary factors, in particular a traditional food pattern, are associated with telomere length and may contribute to the extended longevity of elderly Costa Ricans.

Association of macronutrients and dietary patterns with risk of systemic lupus erythematosus in the Black Women's Health Study.

BACKGROUND: Systemic lupus erythematosus (SLE) affects African-American (AA) women disproportionately. The few prospective studies assessing dietary intake in relation to risk of SLE have been conducted in predominantly white populations and have been null. OBJECTIVES: The present study assessed associations of macronutrients and dietary patterns with risk of SLE in AA women. METHODS: Data from the Black Women's Health Study was collected prospectively via biennial questionnaires starting in 1995. Participants completed a self-administered 68-item FFQ in 1995. Self-reported SLE was verified through medical record review. We used multivariable (MV) Cox regression models to estimate HRs and 95% CIs for macronutrients, carbohydrates, proteins, total fats, PUFAs, ω-3 fatty acids, ω-6 fatty acids, MUFAs, saturated fats, trans fatty acids, Alternative Healthy Eating Index score, vegetable/fruit and meat/fried food dietary patterns, and a reduced rank regression (RRR)-derived dietary pattern in relation to SLE risk. RESULTS: We confirmed a total of 114 incident cases of SLE among 51,934 women during 1995-2015. MVHRs and 95% CIs for the highest quintile of intake versus the lowest were HR: 1.96, 95% CI: 1.02, 3.67 for carbohydrates; HR: 0.66, 95% CI: 0.37, 1.18 for protein; and HR: 0.54, 95% CI: 0.28, 1.01 for total fats. MUFAs, saturated fatty acids, and trans fatty acids were significantly associated with a lower risk of SLE. An RRR-derived factor, rich in fruits and sugar-sweetened drinks and low in margarines and butter, red and processed meats, fried chicken, poultry, and eggs, which explained 53.4% of the total variation of macronutrients, was the only food pattern associated with increased SLE risk (HR: 1.88, 95% CI: 1.06, 3.35). CONCLUSION: These analyses suggest that a diet high in carbohydrates and low in fats is associated with increased SLE risk in AA women.

Starchy Vegetables and Metabolic Syndrome in Costa Rica.

Only a few studies primarily examined the associations between starchy vegetables (other than potatoes) and metabolic syndrome (MetS). We aimed to evaluate the association between starchy vegetables consumption and MetS in a population-based sample of Costa Rican adults. We hypothesized that a higher overall intake of starchy vegetables would not be associated with higher MetS prevalence. In this cross-sectional study, log-binomial regression models were used to estimate prevalence ratios (PRs) of MetS across quintiles of total, unhealthy, healthy starchy vegetables, and individual starchy vegetables (potatoes, purple sweet potatoes, etc.), among 1881 Costa Rican adults. Least square means and 95% confidence intervals (CIs) from linear regression models were estimated for each MetS component by categories of starchy vegetable variables. Higher intakes of starchy vegetables were associated with a higher prevalence of MetS in crude models, but no significant trends were observed after adjusting for confounders. A significant inverse association was observed between total starchy and healthy starchy vegetables consumption and fasting blood glucose. In this population, starchy vegetables might be part of a healthy dietary pattern.

Associations between polygenic risk score for age at menarche and menopause, reproductive timing, and serum hormone levels in multiple race/ethnic groups.

OBJECTIVE: We assessed associations of genetic loci that contribute to age at menarche and menopause with sentinel menopausal traits in multiple race/ethnic groups. METHODS: Genetic data from the Study of Women's Health Across the Nation include 738 White, 366 Black, 139 Chinese, and 145 Japanese women aged 42 to 52 at baseline. We constructed standardized polygenic risk scores (PRSs) using single nucleotide polymorphisms identified from large-scale genome-wide association studies meta-analyses of ages at menopause and menarche, evaluating associations with each trait within each race/ethnic group. RESULTS: Menopause PRS was significantly associated with age at menopause in White women after Bonferroni correction (P < 0.004) and nominally associated in Chinese and Japanese women (P < 0.05) (7.4-8.5 mo delay for one standard deviation [SD] increase in PRS). Menarche PRS was significantly associated with age at menarche in White (P < 0.004) and nominally associated in Black and Japanese women (P < 0.05) (2.6-4.8 mo delay for one SD increase). In White women, menarche and menopause PRSs were significantly associated (P < 0.004) with shorter and longer (5.9 and 9.6 mo for one SD increase) reproductive lifespans, respectively, and menopause PRS with a longer menopausal transition (7.1 mo for one SD increase). We observed a significant positive association (P < 0.004) between menopause PRS and E2 level 2 years before menopause and a nominal association (P < 0.05) 2 years after menopause in Japanese women. CONCLUSIONS: In addition to menopausal timing, PRSs associated with onset and ending of reproductive life were associated with reproductive lifespan, length of the menopausal transition, and E2 levels in different race/ethnic groups.

Genetic architecture of type 2 diabetes and its shared genetic component with low birth weight in African Americans.

PURPOSE OF REVIEW: Recent large-scale multiancestry efforts has contributed to our knowledge of the hereditary basis of type 2 diabetes (T2D). The present review will summarize findings of the genetic basis of T2D in African Americans, a population group with a disproportionate burden of this disease. RECENT FINDINGS: To date, >400 risk genetic variants have been found to be associated with the risk of T2D across populations of different ancestries. Although these findings are based on primarily European-ancestry populations, most of the identified loci show similar associations in African Americans. Ancestry-specific analyses including genome-wide associations studies (GWAS) in African Americans, Africans; as well as admixture mapping scans in African Americans have identified additional risk variants and genomic loci associate with the risk of T2D. These efforts have also uncovered new genetic links between low birth weight and T2D. In particular, admixture mapping approaches have identified a shared genetic ancestry component of both phenotypic traits in African Americans. SUMMARY: Recent findings have helped us to better understand the genetic basis of T2D in African Americans. Of particular interest are new genetic discoveries linking low birth weight and T2D, two conditions with a much higher prevalence in African Americans compared to U.S. whites. Continuing work, including large-scale sequencing efforts would add to our knowledge of the genetic architecture of T2D in African Americans, as well as genetic links with other conditions.

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

BACKGROUND: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. METHODS: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. RESULTS: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. CONCLUSION: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.

Genetic variants in anti-Müllerian hormone-related genes and breast cancer risk: results from the AMBER consortium.

PURPOSE: Circulating anti-Müllerian hormone (AMH) levels are positively associated with time to menopause and breast cancer risk. We examined breast cancer associations with single nucleotide polymorphisms (SNPs) in the AMH gene or its receptor genes, ACVR1 and AMHR2, among African American women. METHODS: In the AMBER consortium, we tested 65 candidate SNPs, and 1130 total variants, in or near AMH, ACVR1, and AMHR2 and breast cancer risk. Overall, 3649 cases and 4230 controls contributed to analyses. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were calculated using multivariable logistic regression. RESULTS: After correction for multiple comparisons (false-discovery rate of 5%), there were no statistically significant associations with breast cancer risk. Without correction for multiple testing, four candidate SNPs in ACVR1 and one near AMH were associated with breast cancer risk. In ACVR1, rs13395576[C] was associated with lower breast cancer risk overall (OR 0.84; 95% CI 0.72, 0.97) and for ER+ disease (OR 0.75; CI 0.62, 0.89) (p < 0.05). Rs1220110[A] and rs1220134[T] each had ORs of 0.89-0.90 for postmenopausal and ER+ breast cancer (p ≤ 0.03). Conversely, rs1682130[T] was associated with higher risk of ER+ breast cancer (OR 1.17; 95% CI 1.04, 1.32). Near AMH, rs6510652[T] had ORs of 0.85-0.90 for breast cancer overall and after menopause (p ≤ 0.02). CONCLUSIONS: The present results, from a large study of African American women, provide limited support for an association between AMH-related polymorphisms and breast cancer risk and require replication in other studies.

Night Shift Work and Fecundability in Late Reproductive-Aged African American Women.

Background: We estimated the association between night shift work and fecundability among African American women. Methods: Black Women's Health Study participants (n = 560) aged 30-45 years reported their history of night shift work in 2005. Time to pregnancy for all pregnancies resulting in a livebirth was reported in 2011. We estimated the fecundability ratio (FR) and 95% confidence interval (CI) using proportional probabilities regression, accounting for multiple observations of individual women using generalized estimating equations. Results: We observed 4,417 months of pregnancy attempt time resulting in 390 births. After adjustment for covariates, women who reported ever working night shifts had 20% lower fecundability compared with those who never reported night shift work (FR = 0.80, 95% CI: 0.59-1.04). The FR for women reporting night shift work with a frequency of ≥1 time per month and a duration of ≥2 years was 0.65 (95% CI: 0.47-0.94) relative to women reporting no shift work. We observed a decrease in fecundability associated with ever working night shifts (FR = 0.74, 95% CI: 0.56-0.96) among women aged ≥35 years, but not among younger women (FR = 1.33, 95% CI: 0.78-2.28). Conclusion: A history of working night shifts was associated with reduced fecundability among older reproductive-aged African American women attempting pregnancy.

A Prospective Analysis of Intake of Red and Processed Meat in Relation to Pancreatic Cancer among African American Women.

BACKGROUND: African Americans have the highest incidence of pancreatic cancer of any racial/ethnic group in the United States. There is evidence that consumption of red or processed meat and foods containing saturated fats may increase the risk of pancreatic cancer, but there is limited evidence in African Americans. METHODS: Utilizing the Black Women's Health Study (1995-2018), we prospectively investigated the associations of red and processed meat and saturated fats with incidence of pancreatic adenocarcinoma (n = 168). A food frequency questionnaire was completed by 52,706 participants in 1995 and 2001. Multivariable-adjusted HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. We observed interactions with age (P interaction = 0.01). Thus, results were stratified at age 50 (<50, ≥50). RESULTS: Based on 148 cases among women aged ≥50 years, total red meat intake was associated with a 65% increased pancreatic cancer risk (HRQ4 vs. Q1 = 1.65; 95% CI, 0.98-2.78; P trend = 0.05), primarily due to unprocessed red meat. There was also a nonsignificant association between total saturated fat and pancreatic cancer (HRQ4 vs. Q1 = 1.85; 95% CI, 0.92-3.72; P trend = 0.08). Red meat and saturated fat intakes were not associated with pancreatic cancer risk in younger women, and there was no association with processed meat in either age group. CONCLUSIONS: Red meat-specifically, unprocessed red meat-and saturated fat intakes were associated with an increased risk of pancreatic cancer in African-American women aged 50 and older, but not among younger women. IMPACT: The accumulating evidence-including now in African-American women-suggests that diet, a modifiable factor, plays a role in the etiology of pancreatic cancer, suggesting opportunities for prevention.

A prospective study of yogurt and other dairy consumption in relation to incidence of type 2 diabetes among black women in the USA.

BACKGROUND: Yogurt consumption and low-fat dairy consumption have been associated with reduced incidence of type 2 diabetes (T2D) in some studies. OBJECTIVE: We assessed the relation of yogurt and other dairy consumption to incidence of T2D in black women, a population group with a disproportionately high incidence of T2D. METHODS: The Black Women's Health Study has followed 59,000 US black women since 1995 through biennial questionnaires which update health information. Each questionnaire inquired about doctor-diagnosed diabetes in the previous 2 y. FFQs completed by participants in 1995 and 2001 provided information on yogurt and other dietary intake. HRs with 95% CIs for yogurt (nonfrozen or frozen) and other dairy consumption in relation to incident T2D (n = 8061 cases) were estimated with Cox proportional hazards regression, controlling for risk factors for T2D. RESULTS: The HR for consumption of ≥1 serving of yogurt/d relative to <1 serving/mo was 0.99 (95% CI: 0.87, 1.13, P trend = 0.65) after control for dietary and nondietary risk factors for T2D. The multivariable HR was 0.97 (95% CI: 0.75, 1.27; P trend = 0.74) for 2 or more servings/d of low-fat dairy other than yogurt relative to <1 serving/mo and 1.06 (95% CI: 0.91, 1.25, P trend = 0.36) for 2 or more servings/d of regular dairy relative to <1 serving/mo. CONCLUSION: Results from this study do not support an inverse association of yogurt consumption or other dairy consumption with T2D risk in black women.

Accelerometer-measured Physical Activity, Reproductive Hormones, and DNA Methylation.

INTRODUCTION/PURPOSE: Limited studies have examined the association of physical activity with reproductive hormones, DNA methylation, and pubertal status among adolescents. METHODS: Among 248 boys and 271 girls, we estimated daily physical activity levels based on 7 d of wrist-worn accelerometer data. We used an isotemporal substitution paradigm and sex-stratified regression models to examine the association of physical activity levels with 1) testosterone, cortisol, progesterone, and androstenedione concentrations; 2) DNA methylation of long interspersed nucleotide (LINE-1) repeats and the genes H19, hydroxysteroid (11-Beta) dehydrogenase 2 (HSD11B2), and peroxisome proliferator-activated receptor alpha (PPARA) from blood leukocytes; and 3) Tanner stages, adjusted for age, BMI, and socioeconomic status. RESULTS: In boys, substituting 30 min of moderate physical activity for 30 min of sedentary behavior per day was associated with 29% (-49%, 0%) of lower testosterone and 29% (4%, 61%) of higher progesterone. Substituting 30 min of light physical activity for sedentary behavior was associated with 13% (-22%, -2%) of lower progesterone. Among girls, 30 min of additional sedentary behavior was associated with 8% (-15%, 0%) of lower testosterone and 24% (8%, 42%) of higher progesterone concentrations. Substituting 30 min of moderate physical activity for sedentary behavior was associated with 15% (0%, 31%) of higher cortisol, whereas substituting the same amount of light physical activity for sedentary behavior was associated with 22% (-39%, 0%) of lower progesterone. Substituting 30 min of vigorous physical activity for sedentary behavior per day was associated with almost six times higher levels (5.83, 95% confidence interval = 1.79-9.86) of HSD11B2 methylation in boys. CONCLUSIONS: Accelerometer-measured daily physical activity was associated with reproductive hormones and HSD11B2 DNA methylation, differed by sex and activity intensity levels.