Using genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes.

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations.

Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction.

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10-8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66-7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

Feasibility of precision smoking treatment in a low-income community setting: results of a pilot randomized controlled trial in The Southern Community Cohort Study.

BACKGROUND: The feasibility of precision smoking treatment in socioeconomically disadvantaged communities has not been studied. METHODS: Participants in the Southern Community Cohort Study who smoked daily were invited to join a pilot randomized controlled trial of three smoking cessation interventions: guideline-based care (GBC), GBC plus nicotine metabolism-informed care (MIC), and GBC plus counseling guided by a polygenic risk score (PRS) for lung cancer. Feasibility was assessed by rates of study enrollment, engagement, and retention, targeting > 70% for each. Using logistic regression, we also assessed whether feasibility varied by age, sex, race, income, education, and attitudes toward precision smoking treatment. RESULTS: Of 92 eligible individuals (79.3% Black; 68.2% with household income < $15,000), 67 (72.8%; 95% CI 63.0-80.9%) enrolled and were randomized. Of these, 58 (86.6%; 95% CI 76.4-92.8%) engaged with the intervention, and of these engaged participants, 43 (74.1%; 95% CI 61.6-83.7%) were retained at 6-month follow-up. Conditional on enrollment, older age was associated with lower engagement (OR 0.83, 95% CI 0.73-0.95, p = 0.008). Conditional on engagement, retention was significantly lower in the PRS arm than in the GBC arm (OR 0.18, 95% CI 0.03-1.00, p = 0.050). No other selection effects were observed. CONCLUSIONS: Genetically informed precision smoking cessation interventions are feasible in socioeconomically disadvantaged communities, exhibiting high enrollment, engagement, and retention irrespective of race, sex, income, education, or attitudes toward precision smoking treatment. Future smoking cessation interventions in this population should take steps to engage older people and to sustain participation in interventions that include genetic risk counseling. TRIAL REGISTRATION: ClinicalTrials.gov No. NCT03521141, Registered 27 April 2018, https://www. CLINICALTRIALS: gov/study/NCT03521141.

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.

The Role of Spirituality on Physical Activity and Sleep Among African American Long-Term Breast Cancer Survivors.

BACKGROUND: African Americans with chronic conditions have reported the importance of spirituality in their lives. Aspects of spirituality have been shown to be related to physical activity (PA) and sleep, and PA and sleep affect quality of life (QOL). This study examined the association between spirituality, PA, and sleep in long-term African American breast cancer survivors. METHODS: This cross-sectional study included 323 breast cancer survivors who previously participated in a case-only study. During 2015-2016, participants completed a questionnaire focused on survivorship that used validated measures for spirituality, PA, and sleep. Adjusted binary and multinomial logistic regression models estimated odds ratios (aORs) and 95% confidence intervals (CIs) for the associations of spirituality with total PA, meeting PA guidelines, sleep duration, and sleep medication. RESULTS: The mean age at diagnosis was 54.8 (SD = 9.89) years. The range of spirituality scores was 7-48 (median = 44). Among participants who had a score ≥ 44, 59% had high total PA, 61% met PA guidelines, 59% had high sleep duration, and 55% did not use sleep medication. Higher spirituality score was associated with higher total PA (aOR for ≥ 681 min/week: 1.90, 95% CI: 1.03-3.50), meeting PA guidelines (aOR: 1.78, 95% CI: 1.06-2.98), sleep duration > 7 h/night (aOR: 1.72, 95% CI 1.05-2.83), and lack of sleep medication use (aOR: 0.45, 95% CI: 0.24-0.84). CONCLUSION: In African American long-term breast cancer survivors, a higher spirituality score increased the likelihood of greater PA and high sleep duration. These results indicate that interventions surrounding spirituality may benefit the QOL of African American breast cancer survivors.

Lifetime Interpersonal Violence or Abuse and Diabetes Rates by Sex and Race.

INTRODUCTION: Lifetime exposure to interpersonal violence or abuse has been associated with several chronic diseases, including adult-onset diabetes, yet this pattern has not been confirmed by sex and race within a large cohort. METHODS: Data from the Southern Community Cohort Study collected between 2002-2009 and 2012-2015 were used to explore the relationship between lifetime interpersonal violence or abuse and diabetes (N=25,251). Prospective analyses of lower-income people living in the southeastern U.S. were conducted in 2022 to examine the risk of adult-onset diabetes associated with lifetime interpersonal violence or abuse by sex and race. Lifetime interpersonal violence or abuse was defined as (1) physical or psychological violence, threats, or abuse in adulthood (adult interpersonal violence or abuse) and (2) childhood abuse or neglect. RESULTS: After adjustment for potentially confounding factors, adult interpersonal violence or abuse was associated with a 23% increased risk of diabetes (adjusted hazard ratio=1.23; 95% CI=1.16, 1.30). Diabetes risks associated with childhood abuse or neglect were 15% (95% CI=1.02, 1.30) for neglect and 26% (95% CI=1.19, 1.35) for abuse. When combining adult interpersonal violence or abuse and childhood abuse or neglect, the risk of diabetes was 35% higher (adjusted hazard ratio=1.35; 95% CI=1.26, 1.45) than those experiencing no violence, abuse, or neglect. This pattern held among Black and White participants, and among women and men. CONCLUSIONS: Both adult interpersonal violence or abuse and childhood abuse or neglect increased the risk of adult-onset diabetes in a dose-dependent pattern for men and women, and by race. Intervention and prevention efforts to reduce adult interpersonal violence or abuse and childhood abuse or neglect could not only reduce the risk of lifetime interpersonal violence or abuse but may also reduce one of the most prevalent chronic diseases, adult-onset diabetes.

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.

BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility. OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry. DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. RESULTS AND LIMITATIONS: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4). CONCLUSIONS: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. PATIENT SUMMARY: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.

Black Women's Perspectives on Breast Cancer Risk Assessment.

PURPOSE: The aim of this study was to gather the perspectives of Black women on breast cancer risk assessment through a series of one-on-one interviews. METHODS: The authors conducted a cross-sectional qualitative study consisting of one-on-one semistructured telephone interviews with Black women in Tennessee between September 2020 and November 2020. Guided by the Health Belief Model, qualitative analysis of interview data was performed in an iterative inductive and deductive approach and resulted in the development of a conceptual framework to depict influences on a woman's decision to engage with breast cancer risk assessment. RESULTS: A total of 37 interviews were completed, and a framework of influences on a woman's decision to engage in breast cancer risk assessment was developed. Study participants identified several emerging themes regarding women's perspectives on breast cancer risk assessment and potential influences on women's decisions to engage with risk assessment. Much of women's decision context was based on risk appraisal (perceived severity of cancer and susceptibility of cancer), emotions (fear and trust), and perceived risks and benefits of having risk assessment. The decision was further influenced by modifiers such as communication, the risk assessment protocol, access to health care, knowledge, and health status. Perceived challenges to follow-up if identified as high risk also influenced women's decisions to pursue risk assessment. CONCLUSIONS: Black women in this study identified several barriers to engagement with breast cancer risk assessment. Efforts to overcome these barriers and increase the use of breast cancer risk assessment can potentially serve as a catalyst to address existing breast cancer disparities. Continued work is needed to develop patient-centric strategies to overcome identified barriers.

Barriers to Implementation of Breast Cancer Risk Assessment: The Health Care Team Perspective.

PURPOSE: To assess health care professionals' perceptions of barriers to the utilization of breast cancer risk assessment tools in the public health setting through a series of one-on-one interviews with health care team members. METHODS: We conducted a cross-sectional qualitative study consisting of one-on-one semistructured telephone interviews with health care team members in the public health setting in the state of Tennessee between May 2020 and October 2020. An iterative inductive-deductive approach was used for qualitative analysis of interview data, resulting in the development of a conceptual framework to depict influences of provider behavior in the utilization of breast cancer risk assessment. RESULTS: A total of 24 interviews were completed, and a framework of influences of provider behavior in the utilization of breast cancer risk assessment was developed. Participants identified barriers to the utilization of breast cancer risk assessment (knowledge and understanding of risk assessment tools, workflow challenges, and availability of personnel); patient-level barriers as perceived by health care team members (psychological, economic, educational, and environmental); and strategies to increase the utilization of breast cancer risk assessment at the provider level (leadership buy-in, training, supportive policies, and incentives) and patient level (improved communication and better understanding of patients' perceived cancer risk and severity of cancer). CONCLUSIONS: Understanding barriers to implementation of breast cancer risk assessment and strategies to overcome these barriers as perceived by health care team members offers an opportunity to improve implementation of risk assessment and to identify a racially, geographically, and socioeconomically diverse population of young women at high risk for breast cancer.

COVID-19 Vaccination: Comparison of Attitudes, Decision-Making Processes, and Communication among Vaccinated and Unvaccinated Black Americans.

BACKGROUND: COVID-19 vaccination rates remain suboptimal among Black Americans who disproportionately experience higher hospitalization and death rates than White Americans. METHODS: We conducted a multi-method (interviews and surveys) study among 30 Black Americans (n = 16 vaccinated, n = 14 unvaccinated) to explore factors related to vaccination hesitancy, decision-making processes, and communication related to uptake. Participants were recruited by using community-driven approaches, including partner collaborations. Thematic analysis was used to analyze qualitative data, and descriptive and bivariate analysis was used for quantitative data. RESULTS: Of those unvaccinated, 79% (n = 11) stated they were delaying and 21% (n = 3) were declining vaccination indefinitely. When asked about the likelihood of vaccine initiation in 6 months and 12 months, 29% (n = 4) and 36% (n = 5), respectively, stated that they would receive the vaccine. The following themes emerged: (1) COVID-19 vaccination hesitancy exists on a continuum; (2) varied decision-making processes for COVID-19 vaccination; (3) motivators among vaccinated individuals; (4) barriers among unvaccinated individuals; (5) retrieving and navigating vaccine information within the COVID-19 infodemic; and (6) parent perspectives on child vaccination. CONCLUSIONS: Findings suggest that vaccinated and unvaccinated participants had similar and dissimilar perspectives in decision-making processes and vaccine concerns as shown in the Decision-making Processes for the COVID-19 vaccination (DePC) model. Based on these findings, future studies should further explore how factors influencing decision-making can lead to divergent outcomes for COVID-19 vaccination.

Association of Psychosocial Factors on COVID-19 Testing among YWCA Service Recipients.

The purpose of this study was to examine how psychosocial factors affect receipt of COVID-19 testing among Black and Hispanic women. In this cross-sectional study of Black and Hispanic women who received services from the YWCAs in Atlanta, El Paso, Nashville, and Tucson between 2019 and 2021 (n = 662), we used Patient-Reported Outcomes Measurement Information Systems (PROMIS) item bank 1.0 short forms to examine the impact of psychosocial factors (i.e., depression, anxiety, social isolation, instrumental support, emotional support, and companionship) on COVID-19 testing. Multivariable logistic regression models were used to estimate odds ratios and 95% confidence intervals for receipt of a COVID-19 test associated with psychosocial factors while adjusting for confounders. There was little effect of moderate/severe depressions or anxiety on receipt of COVID-19 testing. Black (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.26-1.29) and Hispanic (OR 0.61, 95% CI 0.38-0.96) women with high levels of emotional support were less likely to receive the COVID-19 test. While high levels of instrumental support was associated with less likely receipt of the COVID-19 test among Black women (OR 0.75, 95% CI 0.34-1.66), it was associated with more likely receipt among Hispanic women (OR 1.19, 95% CI 0.74-1.92). Our findings suggest that certain psychosocial factors influence one's decision to get a COVID-19 test which can be useful in encouraging preventive healthcare such as screening and vaccination.

Patterns of Physical Activity and the Role of Obesity and Comorbidities Among Long-term African American Breast Cancer Survivors.

PURPOSE: Physical activity (PA) has many health benefits for cancer survivors, but little research has examined patterns and correlates in African American women, who have a higher burden of comorbidities and obesity. We examined PA types and patterns overall and by obesity and comorbidities among long-term (> 5 years) breast cancer survivors. METHODS: This cross-sectional study included 323 women who were previous participants of a case-only study in three southeastern states. Women completed a survivorship-focused questionnaire using validated measures to collect data on cancer treatment, PA (recreational, household, transportation) and other lifestyle factors, and comorbidities. Logistic regression models estimated adjusted ORs and 95% CIs for total PA (all three types, categorized as tertiles) and meeting PA guidelines (> 150 min/week of exercise). RESULTS: The mean age of women was 59.1 years (range 27.9-79.5). The most frequent PA types (≥ 1/month) included routine household cleaning (92.9%), shopping (94.7%), walking slowly (42.1%), and walking briskly (40.6%). Less than 40% met PA guidelines. Women with more total comorbidities, arthritis, and obesity had lower levels of total PA (minutes/week) and/or recreational PA. In adjusted models, BMI ≥ 35 kg/m2 was associated with reduced odds of total PA (OR = 0.33, 95% CI 0.12-0.88, highest tertile). Arthritis was associated with reduced odds of meeting PA guidelines (OR = 0.61, 95% CI 36-1.05). CONCLUSIONS: Close to 60% of African American breast cancer survivors did not meet PA guidelines based on recreational PA participation. Household PA was an important source of PA. Comorbidities and obesity were associated with both reduced total PA and not meeting PA guidelines.

Psychosocial impact of COVID-19 among adults in the southeastern United States.

Limited research has explored the mental health impact of coronavirus disease 2019 (COVID-19) in the U.S., especially among Black and low-income Americans who are disproportionately affected by COVID-19. To address this gap in the literature, we investigated factors associated with depressive and anxiety symptoms during the pandemic. From October to December 2020, over 4400 participants in the Southern Community Cohort Study (SCCS) completed a survey about the impact of the pandemic. The SCCS primarily enrolled adults with low income in 12 southeastern states. We used polytomous unconditional logistic regression to investigate factors associated with depressive and anxiety symptoms. About 28% of respondents reported mild or moderate/severe depressive symptoms and 30% reported mild or moderate/severe anxiety symptoms. Respondents in fair/poor health had significantly higher odds of moderate/severe depression and anxiety than those in very good/excellent health (depression: odds ratio (OR) = 4.72 [95% confidence interval (CI): 3.57-6.23]; anxiety: OR = 4.77 [95%CI: 3.63-6.28]). Similarly, living alone was associated with higher odds of moderate/severe depression and anxiety (depression: OR = 1.74 [95%CI: 1.38-2.18]; anxiety: OR = 1.57 [95%CI: 1.27-1.95]). Individuals whose physical activity or vegetable/fruit consumption decreased since the start of the pandemic also had higher odds of moderate/severe depression and anxiety. Results overall suggest that individuals in fair/poor health, living alone, and/or experiencing decreased physical activity and vegetable/fruit consumption have higher risk of depressive and anxiety symptoms. Clinical and public health interventions are needed to support individuals experiencing depression and anxiety during the pandemic.

Dispositional optimism and optimistic bias: Associations with cessation motivation, confidence, and attitudes.

OBJECTIVE: To test whether 2 conceptually overlapping constructs, dispositional optimism (generalized positive expectations) and optimistic bias (inaccurately low risk perceptions), may have different implications for smoking treatment engagement. METHOD: Predominantly Black, low-income Southern Community Cohort study smokers (n = 880) self-reported dispositional optimism and pessimism (Life Orientation Test-Revised subscales: 0 = neutral, 12 = high optimism/pessimism), comparative lung cancer risk (Low/Average/High), and information to calculate objective lung cancer risk (Low/Med/High). Perceived risk was categorized as accurate (perceived = objective), optimistically-biased (perceived < objective), or pessimistically-biased (perceived > objective). One-way ANOVAs tested associations between dispositional optimism/pessimism and perceived risk accuracy. Multivariable logistic regressions tested independent associations of optimism/pessimism and perceived risk accuracy with cessation motivation (Low/High), confidence (Low/High), and precision treatment attitudes (Favorable/Unfavorable), controlling for sociodemographics and nicotine dependence. RESULTS: Mean dispositional optimism/pessimism scores were 8.41 (SD = 2.59) and 5.65 (SD = 3.02), respectively. Perceived lung cancer risk was 38% accurate, 27% optimistically-biased, and 35% pessimistically-biased. Accuracy was unrelated to dispositional optimism (F(2, 641) = 1.23, p = .29), though optimistically-biased (vs. pessimistically-biased) smokers had higher dispositional pessimism (F(2, 628) = 3.17, p = .043). Dispositional optimism was associated with higher confidence (Adjusted odds ratio [AOR] = 1.71, 95% CI [1.42, 2.06], p < .001) and favorable precision treatment attitudes (AOR = 1.66, 95% CI [1.37, 2.01], p < .001). Optimistically-biased (vs. accurate) risk perception was associated with lower motivation (AOR = .64, 95% CI [.42, .98], p = .041) and less favorable precision treatment attitudes (AOR = .59, 95% CI [.38, .94], p = .029). CONCLUSIONS: Dispositional optimism and lung cancer risk perception accuracy were unrelated. Dispositional optimism was associated with favorable engagement-related outcomes and optimistically-biased risk perception with unfavorable outcomes, reinforcing the distinctiveness of these constructs and their implications for smoking treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Development of a Theory-Based, Culturally Appropriate Message Library for Use in Interventions to Promote COVID-19 Vaccination Among African Americans: Formative Research.

BACKGROUND: Disparities in COVID-19 incidence, hospitalization, and mortality rates among African Americans suggest the need for targeted interventions. Use of targeted, theory-driven messages in behavioral and communication interventions could empower African Americans to engage in behaviors that prevent COVID-19. OBJECTIVE: To address this need, we performed a formative study that aimed to develop and design a culturally appropriate, theory-based library of messages targeting concerns around COVID-19 vaccines that could be used in behavioral and communication interventions for African Americans. METHODS: Message development occurred between January 2021 and February 2022. Initial messages were designed by a multidisciplinary team of researchers, community leaders, and community members. Kreuter's 5 strategies (ie, linguistic, peripheral, evidential, sociocultural, and constituent-involving strategies) were used to achieve cultural appropriateness. After forming a community-academic partnership, message development occurred in 4 phases: (1) adaptation of a message library using the literature, (2) review by 6 clinical and research experts for content validation, (3) input and review by a 6-member community advisory panel (CAP), and (4) message pretesting with African Americans via semistructured interviews in a qualitative study. RESULTS: Themes from the semistructured interviews among 30 African Americans were as follows: (1) community reactions to the messages, (2) community questions and information needs, (3) suggestions for additional content, and (4) suggestions to improve comprehension, relevance, and trustworthiness. Feedback from the CAP, community members, and scientific experts was used by members of the community-academic partnership to iteratively update message content to maximize cultural appropriateness. The final message library had 18 message subsets for adults and 17 message subsets for parents and caregivers of children. These subsets were placed into 3 categories: (1) vaccine development, (2) vaccine safety, and (3) vaccine effectiveness. CONCLUSIONS: We used a 4-phase, systematic process using multiple community engagement approaches to create messages for African Americans to support interventions to improve COVID-19 vaccination rates among adults and children. The newly developed messages were deemed to be culturally appropriate according to experts and members of the African American community. Future research should evaluate the impact of these messages on COVID-19 vaccination rates among African Americans.

Avoidance of Emergency Care in the Southeastern United States During the COVID-19 Pandemic.

In a low-income cohort in the Southeastern United States, 5% of participants avoided emergency medical care during the coronavirus disease 2019 pandemic, primarily due to fear and visitor restrictions. Younger age, self-perceived lower health status, lack of a personal doctor, and decreased income were associated with greater likelihood of deferring emergency care.

Evaluating breast cancer predisposition genes in women of African ancestry.

PURPOSE: Studies conducted primarily among European ancestry women reported 12 breast cancer predisposition genes. However, etiologic roles of these genes in breast cancer among African ancestry women have been less well-investigated. METHODS: We conducted a case-control study in African American women, which included 1117 breast cancer cases and 2169 cancer-free controls, and a pooled analysis, which included 7096 cases and 8040 controls of African descent. Odds ratios of associations with breast cancer risk were estimated. RESULTS: Using sequence data, we identified 61 pathogenic variants in 12 breast cancer predisposition genes, including 11 pathogenic variants not yet reported in previous studies. Pooled analysis showed statistically significant associations of breast cancer risk with pathogenic variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, TP53, NF1, RAD51C, and RAD51D (all P < .05). The associations with BRCA1, PALB2, and RAD51D were stronger for estrogen receptor (ER)-negative than for ER-positive breast cancer (P heterogeneity < .05), whereas the association with CHEK2 was stronger for ER-positive than for ER-negative breast cancer. CONCLUSION: Our study confirmed previously identified associations of breast cancer risk with BRCA1, BRCA2, PALB2, ATM, TP53, NF1, and CHEK2 and provided new evidence to extend the associations of breast cancer risk with RAD51C and RAD51D, which was identified previously in European ancestry populations, to African ancestry women.

A pooled case-only analysis of obesity and breast cancer subtype among Black women in the southeastern United States.

PURPOSE: To evaluate the association between obesity and the relative prevalence of tumor subtypes among Black women with breast cancer (BC). METHODS: We conducted a pooled case-only analysis of 1,793 Black women with invasive BC recruited through three existing studies in the southeastern US. Multivariable case-only polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between obesity, measured by pre-diagnostic body mass index (BMI), and human epidermal growth factor receptor 2 + (HER2 +) and triple negative BC (TNBC) subtype relative to hormone receptor (HR) + /HER2- status (referent). RESULTS: Among 359 premenopausal women, 55.4% of cases were HR + /HER2 -, 20.1% were HER2 + , and 24.5% were TNBC; corresponding percentages among 1,434 postmenopausal women were 59.3%, 17.0%, and 23.6%. Approximately, 50-60% of both pre- and postmenopausal women were obese (BMI > 30 kg/m2), regardless of BC subtype. We did not observe a significant association between obesity and BC subtype. Among postmenopausal women, class I obesity (BMI 35 + kg/m2) was not associated with the development of HER2 + BC (OR 0.69; 95% CI 0.42-1.14) or TNBC (OR 0.93; 95% CI 0.60-1.45) relative to HR + /HER2- tumors. Corresponding estimates among premenopausal women were 1.03 (95% CI 0.43-2.48) and 1.13 (95% CI 0.48-2.64). CONCLUSION: In this large study of Black women with BC, there was no evidence of heterogeneity of BMI by BC subtype.

A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10-4), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10-5; stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10-4; metastatic disease: OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT SUMMARY: A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry.

Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24.

BACKGROUND: We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ. MATERIALS AND METHODS: Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC. RESULTS: CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings. CONCLUSION: We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.