A Comparison of Three Area-Level Indices of Neighborhood Deprivation and Socioeconomic Status and their Applicability to Breast Cancer Mortality.

Neighborhood deprivation indices are widely used in research, but the performance of these indices has rarely been directly compared in the same analysis. We examined the Area Deprivation Index, Neighborhood Deprivation Index, and Yost index, and compared their associations with breast cancer mortality. Indices were constructed for Georgia census block groups using 2011-2015 American Community Survey data. Pearson correlation coefficients and percent agreement were calculated. Associations between each index and breast cancer mortality were estimated among 36,795 women diagnosed with breast cancer using Cox proportional hazards regression. The indices were strongly correlated (absolute value of correlation coefficients > 0.77), exhibited moderate (41.4%) agreement, and were similarly associated with a 36% increase in breast cancer mortality. The similar associations with breast cancer mortality suggest the indices measure the same underlying construct, despite only moderate agreement. By understanding their correlations, agreement, and associations with health outcomes, researchers can choose the most appropriate index for analysis.

Aspirin and nonaspirin nonsteroidal antiinflammatory drug use and occurrence of colorectal adenoma in Black American women.

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women.

A Prospective Analysis of Red and Processed Meat Intake in Relation to Colorectal Cancer in the Black Women's Health Study.

BACKGROUND: Black Americans have the highest incidence of colorectal cancer (CRC) of any racial/ethnic group in the United States. High intake of red and processed meats has been associated with an increased CRC risk in predominately White populations. However, 3 prior studies in Black populations, who have been reported to have high intakes of red and processed meats, have reported no associations. Data on a possible association between CRC risk and SFAs and MUFAs, the primary types of fat in red and processed meats, are inconclusive. OBJECTIVES: We prospectively assessed intakes of processed and unprocessed red meat, SFAs, and MUFAs in relation to CRC risk, utilizing data from the Black Women's Health Study (BWHS, 1995-2018). METHODS: Dietary data were derived from validated FFQs completed in 1995 and 2001. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: Among 52,695 BWHS participants aged 21-69 y at baseline and followed for ≤22 y, 564 women developed incident CRC. Unprocessed red meat intake was associated with a 33% increased CRC risk per 100 g/d (HR: 1.33; 95% CI: 1.03-1.71). Examination of CRC anatomic sites revealed that unprocessed red meat was associated with 2-times increased rectal cancer risk (HR: 2.22; 95% CI: 1.15-4.26). There was no evidence of an interaction with age (pinteraction = 0.4), but unprocessed red meat intake was only associated with a significant increased risk of late-onset CRC (≥50 y of age, HR: 1.41; 95% CI: 1.05-1.88). Processed red meat and total SFA and MUFA intakes were not associated with CRC risk. CONCLUSIONS: Unprocessed red meat intake was associated with an increased CRC risk in the present study, the first positive evidence that red meat plays a role in the etiology of CRC in Black women. The findings suggest prevention opportunities.

Neighborhood disadvantage and individual-level life stressors in relation to breast cancer incidence in US Black women.

BACKGROUND: Research on psychosocial stress and risk of breast cancer has produced conflicting results. Few studies have assessed this relation by breast cancer subtype or specifically among Black women, who experience unique chronic stressors. METHODS: We used prospective data from the Black Women's Health Study, an ongoing cohort study of 59,000 US Black women, to assess neighborhood- and individual-level psychosocial factors in relation to risk of breast cancer. We used factor analysis to derive two neighborhood score variables after linking participant addresses to US Census data (2000 and 2010) on education, employment, income and poverty, female-headed households, and Black race for all households in each residential block group. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for established breast cancer risk factors. RESULTS: During follow-up from 1995 to 2017, there were 2167 incident invasive breast cancer cases (1259 estrogen receptor positive (ER +); 687 ER negative (ER-)). For ER- breast cancer, HRs were 1.26 (95% CI 1.00-1.58) for women living in the highest quartile of neighborhood disadvantage relative to women in the lowest quartile, and 1.24 (95% CI 0.98-1.57) for lowest versus highest quartile of neighborhood socioeconomic status (SES). For ER+ breast cancer, living in the lowest quartile of neighborhood SES was associated with a reduced risk of ER+ breast cancer (HR = 0.83, 95% CI 0.70-0.98). With respect to individual-level factors, childhood sexual abuse (sexual assault ≥ 4 times vs. no abuse: HR = 1.35, 95% CI 1.01-1.79) and marital status (married/living together vs. single: HR = 1.29, 95% CI 1.08-1.53) were associated with higher risk of ER+, but not ER- breast cancer. CONCLUSION: Neighborhood disadvantage and lower neighborhood SES were associated with an approximately 25% increased risk of ER- breast cancer in this large cohort of Black women, even after control for multiple behaviors and lifestyle factors. Further research is need to understand the underlying reasons for these associations. Possible contributing factors are biologic responses to the chronic stress/distress experienced by individuals who reside in neighborhoods characterized by high levels of noise, crime and unemployment or the direct effects of environmental toxins.

Pre- and perinatal factors and incidence of breast cancer in the Black Women's Health Study.

PURPOSE: The purpose of the study was to investigate the association between pre- or perinatal factors and breast cancer risk among African American women. METHODS: Participants in the Black Women's Health Study, a prospective cohort of 59,000 African American women, reported birth weight, preterm birth, twin or triplet status, maternal age at birth, birth order, and having been breastfed during infancy at various times during follow-up from 1997 to 2015. Numbers of incident cases ranged from 312 for breastfed analyses to 1,583 for twin or triplet analyses. Using multivariable Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between each factor and breast cancer risk overall and by estrogen receptor (ER) status. RESULTS: Compared to birth weights of 5 lbs. 8 oz.-8 lbs. 13 oz., low (< 5 lbs. 8 oz.) and high (> 8 lbs. 13 oz.) birth weights were associated with increased breast cancer risk; HRs (95% CI) were 1.19 (0.98-1.44) and 1.26 (0.97-1.63), respectively. Associations were similar by ER status. Having been born to a mother aged ≥ 35 years versus < 20 years was associated with risk of ER+ (HR 1.59, 95% CI 1.10-2.29), but not ER- breast cancer. Other perinatal factors were not associated with breast cancer. CONCLUSION: African American women with a low or high birth weight or born to older mothers may have increased breast cancer risk. Trends towards delayed child birth and higher birth weights, coupled with disproportionately high rates of low birth weight among African Americans, may contribute to increases in breast cancer incidence.

Eyes Wide Open: Sleep as a Potential Contributor to Racial and Ethnic Disparities in Cancer.

U.S. racial and ethnic minoritized groups face disproportionate cancer burdens compared to White Americans. Investigating modifiable factors, such as sleep, that are socially patterned and inequitably distributed by race and ethnicity may advance understanding of cancer disparities and provide intervention opportunities. Emerging data suggest poor sleep health is associated with cancer. Yet, its contribution to racial and ethnic cancer disparities is understudied. In this narrative review, we explored the sleep-cancer relation through a disparities lens. We (i) summarized literature reporting on associations between sleep and cancer among racial and ethnic minority populations; (ii) examined potential sleep-cancer mechanisms; and (iii) discussed future directions. We identified five studies reporting on sleep-cancer associations among minoritized groups. Poor sleep health was associated with aggressive breast cancer among Black women, increased breast cancer risk among Asian women, and increased risk of breast and total cancer among Hispanic/Latinx Americans. Sleep and cancer disparities have similar socioeconomic and behavioral determinants, suggesting racial and ethnic minoritized groups may be vulnerable to poor sleep health and its adverse health impacts. Evidence indicates that the sleep-cancer disparities relation is an emerging, but important area of research that warrants further investigation, as sleep may be an avenue for reducing cancer disparities.

Neighborhood Deprivation and Breast Cancer Mortality Among Black and White Women.

Importance: Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who experience different neighborhood contexts. Accounting for interactions among neighborhood deprivation, race, and other neighborhood characteristics may enhance understanding of the association. Objective: To investigate whether neighborhood deprivation is associated with breast cancer mortality among Black and White women and whether interactions with rurality, residential mobility, and racial composition, which are markers of access, social cohesion, and segregation, respectively, modify the association. Design, Setting, and Participants: This population-based cohort study used Georgia Cancer Registry (GCR) data on women with breast cancer diagnosed in 2010 to 2017 and followed-up until December 31, 2022. Data were analyzed between January 2023 and October 2023. The study included non-Hispanic Black and White women with invasive early-stage (I-IIIA) breast cancer diagnosed between 2010 and 2017 and identified through the GCR. Exposures: The Neighborhood Deprivation Index (NDI), assessed in quintiles, was derived through principal component analysis of 2011 to 2015 block group-level American Community Survey (ACS) data. Rurality, neighborhood residential mobility, and racial composition were measured using Georgia Public Health Department or ACS data. Main Outcomes and Measures: The primary outcome was breast cancer-specific mortality identified by the GCR through linkage to the Georgia vital statistics registry and National Death Index. Cox proportional hazards regression was used to estimate age-adjusted and multivariable-adjusted hazard ratios (HRs) and 95% CIs for the association between neighborhood deprivation and breast cancer mortality. Results: Among the 36 795 patients with breast cancer (mean [SD] age at diagnosis, 60.3 [13.1] years), 11 044 (30.0%) were non-Hispanic Black, and 25 751 (70.0%) were non-Hispanic White. During follow-up, 2942 breast cancer deaths occurred (1214 [41.3%] non-Hispanic Black women; 1728 [58.7%] non-Hispanic White women). NDI was associated with an increase in breast cancer mortality (quintile 5 vs 1, HR, 1.36; 95% CI, 1.19-1.55) in Cox proportional hazards models. The association was present only among non-Hispanic White women (quintile 5 vs 1, HR, 1.47; 95% CI, 1.21-1.79). Similar race-specific patterns were observed in jointly stratified analyses, such that NDI was associated with increased breast cancer mortality among non-Hispanic White women, but not non-Hispanic Black women, irrespective of the additional neighborhood characteristics considered. Conclusions and Relevance: In this cohort study, neighborhood deprivation was associated with increased breast cancer mortality among non-Hispanic White women. Neighborhood racial composition, residential mobility, and rurality did not explain the lack of association among non-Hispanic Black women, suggesting that factors beyond those explored here may contribute to breast cancer mortality in this racial group.

Historical Redlining, Persistent Mortgage Discrimination, and Race in Breast Cancer Outcomes.

Importance: Inequities created by historical and contemporary mortgage discriminatory policies have implications for health disparities. The role of persistent mortgage discrimination (PMD) in breast cancer (BC) outcomes has not been studied. Objective: To estimate the race-specific association of historical redlining (HRL) with the development of BC subtypes and late-stage disease and a novel measure of PMD in BC mortality. Design, Setting, and Participants: This population-based cohort study used Georgia Cancer Registry data. A total of 1764 non-Hispanic Black and White women with a BC diagnosis and residing in an area graded by the Home Owners' Loan Corporation (HOLC) in Georgia were included. Patients were excluded if they did not have a known subtype or a derived American Joint Committee on Cancer stage or if diagnosed solely by death certificate or autopsy. Participants were diagnosed with a first primary BC between January 1, 2010, to December 31, 2017, and were followed through December 31, 2019. Data were analyzed between May 1, 2022, and August 31, 2023. Exposures: Scores for HRL were examined dichotomously as less than 2.5 (ie, nonredlined) vs 2.5 or greater (ie, redlined). Contemporary mortgage discrimination (CMD) scores were calculated, and PMD index was created using the combination of HRL and CMD scores. Main Outcomes and Measures: Estrogen receptor (ER) status, late stage at diagnosis, and BC-specific death. Results: This study included 1764 women diagnosed with BC within census tracts that were HOLC graded in Georgia. Of these, 856 women (48.5%) were non-Hispanic Black and 908 (51.5%) were non-Hispanic White; 1148 (65.1%) were diagnosed at 55 years or older; 538 (30.5%) resided in tracts with HRL scores less than 2.5; and 1226 (69.5%) resided in tracts with HRL scores 2.5 or greater. Living in HRL areas with HRL scores 2.5 or greater was associated with a 62% increased odds of ER-negative BC among non-Hispanic Black women (odds ratio [OR], 1.62 [95% CI, 1.01-2.60]), a 97% increased odds of late-stage diagnosis among non-Hispanic White women (OR, 1.97 [95% CI, 1.15-3.36]), and a 60% increase in BC mortality overall (hazard ratio, 1.60 [95% CI, 1.17-2.18]). Similarly, PMD was associated with BC mortality among non-Hispanic White women but not among non-Hispanic Black women. Conclusions and Relevance: The findings of this cohort study suggest that historical racist policies and persistent discrimination have modern-day implications for BC outcomes that differ by race. These findings emphasize the need for a more nuanced investigation of the social and structural drivers of disparate BC outcomes.

Circadian Disruption and Colorectal Cancer Incidence in Black Women.

BACKGROUND: Animal and experimental studies suggest circadian disruption increases colorectal cancer risk, but evidence in humans is limited. We examined night shift work, chronotype, and residential position within a time zone, proxies for circadian disruption, in relation to colorectal cancer risk. METHODS: Participants in the Black Women's Health Study, a prospective cohort of 59,000 Black American women established in 1995, reported history of night shift work and chronotype on follow-up questionnaires. Residential position within a time zone was estimated using participant addresses at each questionnaire cycle. Number of colorectal cancer cases and follow-up duration varied by analysis depending on timing of exposure assessment, ranging from 204 over the 2005 to 2018 night shift work study period to 452 over the 1995 to 2018 residential position study period. Cox proportional hazards regression was used to estimate multivariable-adjusted HRs and 95% confidence intervals (CI). RESULTS: Compared with never having worked a night shift, working a night shift for ≥10 years was associated with increased colorectal cancer risk (HR = 1.64; 95% CI, 1.01-2.66). However, shorter duration was not. The HR for evening versus morning chronotype was 0.96 (95% CI, 0.73-1.27). Westward position of residence within a time zone was not associated with colorectal cancer risk (HR per 5-degree longitude increase: 0.92; 95% CI, 0.82-1.03). CONCLUSIONS: Our findings suggest a possible increased risk of colorectal cancer associated with long duration night shift work; however, results require confirmation in larger studies. IMPACT: Circadian disruption from long-term night shift work may contribute to colorectal cancer development in Black women.

Attitudes and beliefs about sleep health among a racially and ethnically diverse sample of overweight/obese adults.

OBJECTIVES: To identify and compare how sleep-related attitudes and beliefs vary among racially and ethnically diverse adults with risk factors for cardio-metabolic disease. METHODS: This exploratory qualitative study used online focus group discussions (N = 4 groups among 17 individuals) to collect information about sleep attitudes, beliefs, and practices following participation in the Mindfulness Intervention to Improve Sleep and Reduce Diabetes Risk Among a Diverse Sample in Atlanta (MINDS) study. A rapid analyses approach was used to identify shared themes related to attitudes and beliefs about sleep health and sleep practices across participants. RESULTS: Participants on average were 31years old, 88% female, and identified as Black/African American (52.9%), White (17.7%), Asian (11.8%), and Hispanic (17.7%). Three themes related to attitudes and beliefs about sleep health were identified: prioritization of sleep to improve one's overall health, re-evaluating sleep needs, and interpersonal barriers to sleep. For Black/African American participants prioritizing sleep was coupled with a want to minimize stress as a long-term health promotion strategy, whereas individuals of other races/ethnicities were more focused on the immediate benefits of getting sufficient sleep. Individuals had reappraised their sleep needs and worked to improve their sleep hygiene accordingly, yet still experienced barriers to sleep. The most common barrier to sleep was sharing a sleep environment with someone who had conflicting sleep routines and practices. CONCLUSION: The results of this study suggest perceived benefits of and barriers to sleep vary by race/ethnicity, thus future interventions should be culturally tailored to enhance effectiveness.

What Are the Factors Underlying Colorectal Cancer Health Disparities?

Black Americans have the highest colorectal cancer incidence and mortality rates of any U.S. racial/ethnic group. Warren Andersen and colleagues report that sociocultural, lifestyle, and healthcare factors did not explain the racial disparity in colorectal cancer incidence, but colorectal cancer screening lessened the disparity. While screening is a cornerstone of colorectal cancer prevention, an improved understanding of etiologic factors may inform additional strategies for primary prevention or risk stratification. As important "established" colorectal cancer risk factors have not been corroborated for Black Americans, this begs the question of what other etiologic factors are important for colorectal cancer development in Black American populations. See related article, p. 595.

Racial Disparities and Sex Differences in Early- and Late-Onset Colorectal Cancer Incidence, 2001-2018.

BACKGROUND: Colorectal cancer (CRC) incidence rates have increased in younger individuals worldwide. We examined the most recent early- and late-onset CRC rates for the US. METHODS: Age-standardized incidence rates (ASIR, per 100,000) of CRC were calculated using the US Cancer Statistics Database's high-quality population-based cancer registry data from the entire US population. Results were cross-classified by age (20-49 [early-onset] and 50-74 years [late-onset]), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, American Indian/Alaskan Native, Asian/Pacific Islander), sex, anatomic location (proximal, distal, rectal), and histology (adenocarcinoma, neuroendocrine). RESULTS: During 2001 through 2018, early-onset CRC rates significantly increased among American Indians/Alaskan Natives, Hispanics, and Whites. Compared to Whites, early-onset CRC rates are now 21% higher in American Indians/Alaskan Natives and 6% higher in Blacks. Rates of early-onset colorectal neuroendocrine tumors have increased in Whites, Blacks, and Hispanics; early-onset colorectal neuroendocrine tumor rates are 2-times higher in Blacks compared to Whites. Late-onset colorectal adenocarcinoma rates are decreasing, while late-onset colorectal neuroendocrine tumor rates are increasing, in all racial/ethnic groups. Late-onset CRC rates remain 29% higher in Blacks and 15% higher in American Indians/Alaskan Natives compared to Whites. Overall, CRC incidence was higher in men than women, but incidence of early-onset distal colon cancer was higher in women. CONCLUSIONS: The early-onset CRC disparity between Blacks and Whites has decreased, due to increasing rates in Whites-rates in Blacks have remained stable. However, rates of colorectal neuroendocrine tumors are increasing in Blacks. Blacks and American Indians/Alaskan Natives have the highest rates of both early- and late-onset CRC. IMPACT: Ongoing prevention efforts must ensure access to and uptake of CRC screening for Blacks and American Indians/Alaskan Natives.

Predicted Vitamin D Status and Colorectal Cancer Incidence in the Black Women's Health Study.

BACKGROUND: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations. METHODS: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of participants. We calculated cumulative average predicted vitamin D score at every cycle by averaging scores from cycles up to and including that cycle. Using Cox proportional hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer incidence according to predicted score quartiles. RESULTS: Over follow-up, 488 incident colorectal cancers occurred. Compared with women in the highest quartile of predicted vitamin D score, those in the lowest had an estimated 41% (HR = 1.41; 95% CI, 1.05-1.90) higher colorectal cancer risk. Comparable HRs were 1.44 (95% CI, 1.02-2.01) for colon and 1.34 (95% CI, 0.70-2.56) for rectal cancer. CONCLUSIONS: Low vitamin D status may lead to elevated colorectal cancer risk in African American women. IMPACT: Our findings, taken together with established evidence that vitamin D levels are generally lower in African Americans than other U.S. groups, suggest that low vitamin D status may contribute to the disproportionately high colorectal cancer incidence among African Americans.

Nitrogen-appended N-alkylsulfonamides as inhibitors of gamma-secretase.

The synthesis and gamma-secretase inhibition data for a series of nitrogen-appended N-alkylsulfonamides (11-47) are described. Inhibition of brain Abeta in transgenic mice was demonstrated by two of these compounds (23 and 44).

High-throughput screening and rapid inhibitor triage using an infectious chimeric Hepatitis C virus.

The recent development of a Hepatitis C virus (HCV) infectious virus cell culture model system has facilitated the development of whole-virus screening assays which can be used to interrogate the entire virus life cycle. Here, we describe the development of an HCV growth assay capable of identifying inhibitors against all stages of the virus life cycle with assay throughput suitable for rapid screening of large-scale chemical libraries. Novel features include, 1) the use of an efficiently-spreading, full-length, intergenotypic chimeric reporter virus with genotype 1 structural proteins, 2) a homogenous assay format compatible with miniaturization and automated liquid-handling, and 3) flexible assay end-points using either chemiluminescence (high-throughput screening) or Cellomics ArrayScan™ technology (high-content screening). The assay was validated using known HCV antivirals and through a large-scale, high-throughput screening campaign that identified novel and selective entry, replication and late-stage inhibitors. Selection and characterization of resistant viruses provided information regarding inhibitor target and mechanism. Leveraging results from this robust whole-virus assay represents a critical first step towards identifying inhibitors of novel targets to broaden the spectrum of antivirals for the treatment of HCV.