Publications

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

Having dense breast tissue is a risk factor for breast cancer. We examined growth and development (height, weight, age at which periods started) from early life in relation to breast density at time of mammography. Higher BMI (body mass index) at time of mammography as well as earlier in life are associated with lower mammographic density, with a stronger association for body size closer to the time of mammography. link to online article

Based on data from the same large collaborative analysis in over 18,000 Black women with breast cancer and about 22,000 Black women without cancer as in the previous publication, we used new methods to identify additional genes involved in breast cancer risk. link to online article

Genetic markers that increase the risk of breast cancer even by just a small amount can be combined into a score that can be used to classify women as to whether they are at high, average, or low risk of breast cancer. There is variation among individuals on these markers and variation across populations. Until recently almost all the work on genetic prediction of breast cancer had been done in populations from the U.S. and Europe, and thus did not include some of the genetic markers present in women of more recent African ancestry. Even though the BWHS is large, it takes many times that sample size to go this kind of genetic research. Therefore, after removing identifiers from our data, we combined it with data from a number of other studies of breast cancer in Black women from the U.S., Central America, Nigeria, and Ghana. The combined study was successful in identifying new variants associated with risk of breast cancer and especially with triple negative breast cancer. link to online article

Pack-year smoking history, a measure of how much a person has smoked over time, is currently used as a guideline in determining lung cancer screening eligibility. Results from the present study of women and men from the Southern Community Cohort Study and women from the Black Women’s Health Study suggest that the current US Preventive Services Task Force (USPSTF) guidelines may exclude high-risk individuals, particularly those from racial and ethnic minority groups. The study found that, under the current guideline, only 57.6% of Black patients with lung cancer qualified for screening, while a higher percentage of White patients (74.0%) would have qualified. The study proposes that, instead of using the pack-year smoking calculation, anyone who has smoked for 20 years duration should be screened for lung cancer. The study found that if a 20- year duration of smoking over the lifetime was the threshold for screening then 85.3% of Black lung cancer patients and 82.0% of White lung cancer patients would have been eligible, eliminating the racial disparity in screening eligibility. link to online article

Endometrial cancer incidence rates are increasing. Hypertension is also increasing and has been associated with some cancers. In this study, which combined data from several studies including BWHS, we found that hypertension was associated with an increased risk of endometrial cancer. The association was stronger among premenopausal and perimenopausal women and also among women who had never used postmenopausal hormone therapy. The results suggest that hypertension may be an independent risk factor for endometrial cancer. link to online article

There has been little research examining whether experiences of interpersonal racism are associated with the risk of coronary heart disease (CHD). Based on data from the Black Women’s Health Study, we found a higher risk of CHD among Black women who reported experiences of racism in employment, housing, and with the police than among those who reported no such experiences. We did not find increased risk in relation to perceived racism in everyday life. link to online article

Obesity is one of the known risk factors for multiple myeloma, a blood cancer. In the BWHS, women with high body mass index (BMI>25) in early adulthood have a 57% increased risk of multiple myeloma. Weight control could be a an important in reducing the risk of this disease. link to online article

Adding a polygenic risk score (PRS) to breast cancer risk prediction models created for European-ancestry populations improved the accuracy of the models. We tested the addition of a polygenic risk score developed for African American women (AA-PRS) to the BWHS risk calculator for incident breast cancer in Black Women. The addition of AA-PRS increased the accuracy of the BWHS risk calculator, and it performs similarly to the models in other populations. link to online article

Research has shown that the physiologic response to stress can affect gene expression. Based on breast cancer RNA sequencing data in the Black Women’s Health Study, the top differentially expressed pathways by stress exposure for ER+ cases were related to RNA and protein metabolism, while among ER- cases, they were related to developmental biology, signal transduction, metabolism, and the immune system. Psychosocial stress may affect breast tumor biology through multiple pathways. Changes
in tumor biology and disease progression in relation to stress is an area for further research. link to online article

Physical activity has been shown to be strongly associated with decreased risk of postmenopausal breast cancer, but its association with premenopausal breast cancer is uncertain. In a study of data from 19 cohort studies that included 547,601 premenopausal women, high versus low levels of leisure-time physical activity were associated with reduced risk, suggesting that leisure-time physical activity may lower the risk of premenopausal breast cancer. link to online article

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor to multiple myeloma. Risk factors for MGUS are largely unknown. Hypothesizing that low vitamin D levels might be associated with risk of MGUS, we examined data from the Black Women’s Health Study to assess the association of vitamin D deficiency (level of 25(OH)D less than 20 ng/mL) with risk of MGUS. MGUS was more prevalent among women with vitamin D deficiency but results were not statistically significant. Further study is required to clarify the possible association between vitamin D deficiency and MGUS. link to online article

The investigative team developed a competing-risk model to estimate 5-year breast cancer risk and 10-year non-breast cancer death from women 55 and older in the Black Women’s Health Study, the Women’s Health Initiative-Extension Study (WHI-ES), and the Multiethnic Cohort (MEC), as well as comparing the model performance to existing models. Results showed that the newly developed model performs at least as well as existing breast cancer prediction models and also predicts non-breast cancer death. link to online article

Insomnia disorder is common among Black women. Cognitive-behavioral therapy for insomnia (CBT-I) is considered the gold standard treatment, but there have been few studies of this treatment in minority populations. Culturally tailoring the content of this intervention for Black women may increase the willingness of Black women to seek this treatment and to respond better to the treatment. To study this, we conducted interviews with important stakeholders to determine how we should modify a proven online CBT-I intervention called Sleep Healthy Using the Internet (SHUTi). We were told that it was important to increase the amount of culturally specific visual content in the intervention materials, as well as make the stories told within the program more diverse. As we begin to see more diverse patient populations seeking evidence-based insomnia treatment, the developers of digital health interventions would be wise to consider tailoring elements of their program to recognize cultural differences. link to online article

Sarcoidosis can affect any organ but most commonly affects the lung. It is characterized by granuloma formation. The incidence appears to be greater in women than men and in Black women than other women. Obesity appears to be associated with increased risk and smoking with reduced risk. Several types of infection have been associated with increased risk. Identification of risk factors is needed. link to online article