Publications

The BWHS contributed data to a pooled analysis of 30 cohort studies from North America, Europe, Australia, and Asia to investigate the association between processed meat and unprocessed red meat consumption and risk of bladder cancer. Among 2.5M participants and >20K cases, the study showed a small but significant increase in risk of bladder cancer associated with greater consumption of red and processed meat.link to online article

In the US, legacy per- and polyfluoroalkyl substances, such as PFOS/PFOA, were phased out because of their persistence, bioaccumulation, widespread exposure, and potential health effects, but they were increasingly replaced by shorter-chain alternatives that are less well studied. In a nested case-control study of 12 prospective U.S. cohorts (853 liver cancer cases and 853 controls), PFHpA was positively associated with liver cancer risk (OR 1.78, 95% CI 1.26–2.52), while no associations were observed for the other PFAS evaluated. Associations were substantially stronger among men, for hepatocellular carcinoma, and for cases diagnosed within 10 years of blood collection. Overall, the findings suggest a potential role for the short-chain PFHpA in liver carcinogenesis and warrant further investigation.link to online article

Within the Black Women’s Health Study 2474 participants have been diagnosed with invasive breast cancer. For ER+ cases, there was no association between untreated hypertension and breast cancer specific-death (HR = 0.96, 95% CI = 0.50–1.82); and a strong inverse association between treated hypertension and breast cancer-specific death (HR = 0.53, 95% CI = 0.34–0.83). For ER- cases, there was increased risk of breast cancer specific death among those with untreated hypertension (HR = 2.19, 95% CI = 1.09–4.39), and no association with treated hypertension (HR = 1.32, 95% CI = 0.80–2.19). Conclusion: Black breast cancer patients with hypertension have better survival when their hypertension is treated, possibly due to regular healthcare engagement or the tumor suppressing actions of antihypertensive medications. link to online article

In a prospective cohort study of 48,320 U.S. Black women from the BWHS, perceived discrimination in employment, housing, or with the police were each associated with increased risk of heart failure, with the highest risk observed for women who experienced discrimination due to race in multiple domains. Sexual assault in childhood or adolescence was also associated with elevated of heart failure, with partial attenuation after adjustment for body mass index. link to online article

Individuals from racially minoritized groups are less likely to undergo genetic testing than those from majority groups. We assessed knowledge and attitudes about hereditary cancer genetic testing among >900 BWHS participants with and without breast cancer. Overall knowledge and attitudes were high regardless of prior breast cancer, though some specific gaps in understanding of inheritance, test limitations, and clinical implications of a variant of uncertain significance were noted. link to online article

In a prospective analysis of 57,453 participants in the BWHS, we evaluated the association between cardiometabolic conditions, including obesity, Type 2 diabetes, hypertension, and hypercholesterolemia, and breast cancer risk by ER status and molecular subtypes using competing risk Cox proportional hazards models. Among postmenopausal women, obesity was significantly associated with a higher risk of estrogen receptor-positive (ER+) breast cancer (HR = 1.35, 95% CI = 1.15–1.59), particularly the luminal A-like subtype (HR = 1.54, 95% CI = 1.19–1.98). However, no other cardiometabolic factors were associated with breast cancer subtypes. We also examined women with co-occurrence of 2 to 4 of the cardiometabolic conditions in comparison with women with none of the conditions. Notably, the co-occurrence of ≥ 3 adverse cardiometabolic factors was associated with an increased risk of postmenopausal ER+ but a lower risk of ER− breast cancer: postmenopausal women with three or more conditions experienced a 43% elevated risk of ER+ breast cancer alongside a 38% reduced risk of ER− breast cancer compared to those with optimal health profiles, suggesting a distinct biological role for metabolic–endocrine crosstalk in breast cancer etiology among Black women.link to online article

Compared pre-diagnostic metabolites from 726 hepatocellular carcinoma (HCC) and 126 intrahepatic cholangiocarcinoma (ICC) cases to matched controls to discover metabolic perturbations that are associated with liver cancer risk. Of 1,485 pre-diagnostic metabolites, 600 were associated with HCC risk and none were associated with ICC. Enriched pathways in HCC were consistent with underlying liver dysfunction and included: methylhistidine metabolism, amino acid metabolism, and bile acid biosynthesis. link to online article

Triple negative breast cancer (TNBC) is more common in Black women than White women in the United States. In the AABCG, we investigated genetic associations in 2,335 cases with TNBC, 8,159 ER+ cases, and 9,814 controls. African ancestry was not associated with risk of TNBC. In a case-case analysis, there was a small, statistically significant, increase in African ancestry for those with TNBC compared to those with ER+ breast cancer. We identified potential African ancestry-specific subtype-informative variants at known TNBC risk loci. Future studies are needed to investigate African ancestry-specific pathways to tumor subtype determination. link to online article

Breast cancer risk prediction models have not performed well in Black women. We compared the performance of the BWHS model to two commonly used risk prediction models, the NCI Breast Cancer Risk Assessment Tool and the IBIS Breast Cancer Risk Evaluation Tool. While performance was similar, the BWHS model had better calibration and discriminatory accuracy. Future work includes incorporating mammographic features. link to online article

Preeclampsia is a serious, potentially life-threatening complication of pregnancy which disproportionately impacts Black women. In the BWHS, we found that experiences of interpersonal and institutional racism were associated with an increased risk of preeclampsia. Black women in the highest quartile of a daily racism score had 50% higher odds of developing preeclampsia compared to women in the lowest quartile. Black women who experienced institutional racism (in police, housing, or job) from two domains had 47% higher odds of preeclampsia compared to those with no experience of institutional racism. These findings highlight the role of racism in shaping persistent disparities in Black maternal health in the United States. link to online article

Overweight and obesity are known to increase the risk of many cancers, but their effect on bladder cancer risk is unclear. We pooled data from >2.5M participants (>20,000 cases) in 30 international cohort studies, including BWHS, to assess associations of various measures of body size and risk of bladder cancer, controlling carefully for potential confounding by smoking. Greater BMI, waist circumference, and height were associated with increased risk among males only. link to online article

Polygenic risk scores (PRS) for predicting risk of breast cancer have mostly been developed in women of European descent and generally perform better in this population than in women of African ancestry. PRSs developed in women of African ancestry perform better in this population, but not as well as PRSs developed in women of European ancestry do in women of European ancestry. In the AABCG consortium, we developed PRS models for overall, ER+, ER-, and TNBC. Models which incorporated multiple ancestries and breast cancer subtypes performed best. Women in the highest percentiles of PRS score may benefit from earlier screening. link to online article

The 2023 ACS lung screening recommendations remove the quit-duration criterion, increasing eligibility from 27% (USPSTF) to 33% of smokers. While this improves sensitivity, it lowers specificity and disproportionately benefits White former smokers, widening racial/ethnic disparities in screening eligibility. Overall, more people qualify for screening, but changes are not uniform across groups and may lead to unnecessary screening in some populations. link to online article

The authors explored how living in historically redlined neighborhoods affects fecundability. The study analyzed 818 pregnancy attempts from 674 BWHS participants whose addresses were linked to historical neighborhood (HOLC) grades from the 1930s. Women living in lower-graded neighborhoods (C and D) showed reduced chances of conception compared to those in higher-graded areas (A and B). These findings suggest that historical disinvestment in certain neighborhoods may negatively impact reproductive health. link to online article

The goal of this study was to identify a robust, parsimonious set of R/S measures for common use in U.S. cohort studies. The authors utilized data from the Study on Stress, Spirituality, and Health (SSSH) to compute Exploratory and Confirmatory Factor Analysis (EFA, CFA) of 60 R/S items in a combined sample of American Indian (Strong Heart Study), Black (BWHS), Hispanic/Latino (HC/SOL), South Asian (MASALA), and White (NHS II, GUTS) respondents (n = 16,372). An exploratory factor analysis of 60 R/S items revealed four common dimensions: Positive Religion/Spirituality and Coping, Negative Religious Coping/Spiritual Struggle, Spirituality as Meaning-Purpose-Connection, and Nontheistic Daily Spiritual Experiences. Future work is needed to confirm this model in other data sets, and to demonstrate the external validity of these core R/S constructs in relation to a range of outcomes. link to online article

Few epidemiologic studies have measured the effect of neighborhoods on fertility, particularly in Black women who have higher rates of infertility and lower access to fertility treatment relative to White women. This study prospectively examined the association between neighborhood disadvantage and fecundability (the per-cycle probability of conception) among ~2,100 BWHS participants. The authors found that neighborhood disadvantage was associated with reduced fecundability, particularly among highly educated Black women. The results have important implications for advancing reproductive justice. link to online article

It has been suggested that the gut-liver axis may play an important role in liver cancer. Previous studies have shown that immunological markers of products derived from gut microbes are associated with chronic liver disease, but there is limited research for liver cancer risk. In a nested case-control study of 867 liver cancer cases and matched controls from 12 U.S. cohorts, higher concentrations of bacterial translocation markers—particularly lipopolysaccharide-binding protein (OR=1.48)—were associated with increased liver cancer risk. These findings support a potential role of gut barrier dysfunction in hepatocarcinogenesis. link to online article

We evaluated associations between social and economic attributes of residential neighborhoods and multiple myeloma incidence among Black women living in the United States. Black American women living in areas of concentrated disadvantage and low socioeconomic status had increased risk of multiple myeloma compared to those who lived in more affluent areas, regardless of individual educational attainment. Community reinvestment may offer an opportunity to reduce the increasing burden of MM among Black women. link to online article

Bile acids are produced in the liver and are important for lipid digestion. In the Liver Cancer Pooling Project, we assessed the association between bile acids measured in blood samples and liver cancer risk in 872 cases and 872 matched controls. Pre-diagnostic circulating bile acids, predominantly conjugated bile acids, were associated with liver cancer risk, but primary conjugated bile acids were only associated with hepatocellular carcinoma, not intrahepatic cholangiocarcinoma. These results suggest that bile acids may be important markers of HCC risk. link to online article

In a previous pooled analysis of case-control studies, regular physical inactivity was associated with an increased risk of ovarian cancer. In the Ovarian Cancer in Women of African Ancestry consortium, we evaluated the association of regular physical inactivity and risk of epithelial ovarian cancer among Black women (223 cases; 1,472 controls) and White women (985 cases; 6,212 controls) enrolled in U.S. cohort studies. Women were classified as having regular physical inactivity if they reported no regular weekly moderate or vigorous recreational activity. Regular physical inactivity was not associated with risk of overall ovarian cancer among Black (OR=1.16, 95% CI: 0.83-1.61) or White women (OR=1.03, 95% CI: 0.87-1.23). These results emphasize the complexity of investigating physical activity. link to online article

Diets high in fish consumption and long-chain n-3 polyunsaturated fatty acids (PUFAs) have been associated with reduced risk of colorectal cancer. In BWHS, we evaluated the association between fish, PUFAs, and colorectal cancer risk. High intake of baked fish (~3-4 oz/week) was associated with a 26% reduced risk of incident colorectal cancer, which was notable for proximal colon cancer (HR=0.56). N-3 PUFA intake was also associated with a decreased risk of proximal colon cancer (HR=0.61). This finding suggests that increasing baked fish intake could be a valuable strategy for CRC prevention among Black women. link to online article

Women of African ancestry have the highest incidence of triple-negative breast cancer (TNBC) among all racial and ethnic groups, but have been underrepresented in cancer genomic studies. We used whole-exome sequencing and RNA sequencing to characterize the tumor mutational landscape of TNBC in almost 500 U.S. Black women. The general landscape was similar to what has been shown in Asian and White women, with a few notable differences: TP53 mutations were found in 95% of the tumors and there was a lower than expected frequency of PIK3CA mutation. These findings contribute to the diversity of the knowledgebase on breast cancer genomics and provide novel insights into the disease etiology and therapeutic vulnerability of TNBC in women of African ancestry. link to online article

In an analysis of 4,995 Black women with breast cancer, those who did not obtain regular mammograms prior to diagnosis were 3 times more likely to be diagnosed with Stage 3 or 4 breast cancer compared to Stage 1, and those living below the federal poverty line were almost twice as likely to be diagnosed at Stage 3 or 4, compared to Stage 1. link to online article

Higher CD8+ T-cells have been observed in Black women, compared to White women, across breast cancer subtypes. We examined the association between CD8+ T-cell density in breast tumor tissue and a variant in the Duffy Antigen Receptor for Chemokines in the Women’s Circle of Health study and evaluated the association between this marker and breast cancer risk in the African Ancestry Breast Cancer Genetics Consortium. Women with CC genotype had lower CD8+ T-cell density than those with TT genotype, but this genotype was not associated with overall, ER-negative, or triple-negative breast cancer. link to online article

In this multi-ancestry collaborative study, we used GWAS data to predict protein levels and evaluated their association with overall and ER-specific breast cancer risk. We identified 51 blood proteins associated with breast cancer risk. These proteins are potential biomarkers for breast cancer risk and this work improves our biological understanding of the genetic contribution to breast cancer. link to online article

Sarcoidosis is a systemic inflammatory disorder linked to dysregulation of Vitamin D and calcium metabolism, theoretically increasing the risk of kidney stones. By 2005, a total of 832 BWHS participants (out of 43,718) reported sarcoidosis, and they were twice as likely to report kidney stones compared participants without sarcoidosis. The overall OR of kidney stones was 1.80 (95% CI: 1.25, 2.59), and increased to 1.96 (95% CI: 1.09, 3.52 among women with 3-4 co-occurring metabolic conditions (e.g., obesity, t2d). The findings highlight the importance of monitoring for signs of vitamin D and calcium dysregulation in the management of sarcoidosis, especially among those with co-occurring metabolic conditions. link to online article

In oral health research, participants sometimes respond that they “Don’t know” the answer to questions about their teeth and gums, making analyses challenging. We explored the characteristics of the “Don’t knows” in three data sources: BWHS, PRESTO, and NHANES. In all three samples, they had lower household income, less education, and were less likely to have had a recent dental visit. In sensitivity analyses, excluding the “Don’t knows” led to estimates biased towards the null. link to online article

To evaluate breast cancer risks associated with PV type and location in ATM, BRCA1, BRCA2, CHEK2, and PALB2, we carried out age-adjusted case-control association analysis in 32,247 women with and 32,544 age-matched women without breast cancer from the CARRIERS Consortium population-based and clinical high-risk cohorts. We found that PTVs in exon 11 of BRCA2 are associated with reduced breast cancer risk, later age at diagnosis, and greater risk of ER-negative disease. These differential risks may improve individualized risk prediction and clinical management for women carrying BRCA2 PTVs. link to online article

We conducted a matched nested case-control study within the Liver Cancer Pooling Project to examine whether pre-diagnostic blood levels of per- and polyfluoroalkyl substances (PFAS), including PFOS, PFOA, and PFHxS, were linked to liver cancer risk in 853 cases and 853 controls. Overall, PFAS was not associated with liver cancer risk. However, PFOA showed a sex-specific pattern—positively associated with risk in males (OR: 1.62, 95% CI: 1.07-2.45) and inversely associated in females (OR: 0.68, 95% CI: 0.50-0.92; p-interaction=0.005). The findings suggest no overall PFAS–liver cancer link, but possible sex differences for PFOA warrant further study. link to online article

The BWHS contributed data to the largest-ever genome-wide association study of uterine fibroids. The study identified 46 novel genes associated with fibroids across multi-ancestry and ancestry-stratified GWAS analyses. These genes are significantly enriched in cancer, cell death and survival, reproductive system disease, and cellular growth and proliferation networks. The findings provide evidence for potential candidates for future research on fibroid etiology and targeted therapeutics. link to online article

To improve both human health and the health of our planet, the EAT-Lancet Commission has proposed a planetary health diet (PHD). We aimed to evaluate associations of PHD with all-cause, cardiovascular disease (CVD), and cancer-specific mortality among United States Black females. Women in the quintile representing the highest adherence to PHD were estimated to have an 18% reduction in risk of all-cause mortality [HR = 0.82, 95% confidence interval (CI): 0.71, 0.94] and 26% reduction in CVD-specific mortality (HR = 0.74, 95% CI: 0.55, 0.98), compared with those in the lowest quintile, with similar reductions observed for quintiles 2, 3, and 4. These findings are consistent with results observed in previous studies of white women and women from East Asian countries. link to online article

This large combined analysis included African, Asian, and European ancestry participants. The purpose was to look more closely within genes found to be associated with breast cancer risk in order to identify the precise variants that are involved. The results shed light on mechanisms of breast cancer development, which may lead to improved prevention or treatment. link to online article

Black women are more likely than other U.S. women to develop preeclampsia during pregnancy. We examined whether a certain gene, already know to be involved the higher risk of chronic kidney disease experience by Black Americans, was also involved in preeclampsia. Based on data from the Black Women’s Health Study, there appeared to be no association between that gene and the risk of preeclampsia. link to online article

Diagnosis of endometrial cancer is rising among women under 50. Most recommendations address this diagnosis in women older than 50. It is important to understand risk factors for endometrial cancer in this younger population in order to inform younger women of their risk. We found that the risk factors for older women also apply to younger women. In both groups higher BMI and diagnosis of diabetes were associated with a higher risk of endometrial cancer; we also found that oral contraceptive use and pregnancy were associated with lower risk. Educational efforts should be expanded to include younger women. link to online article