Neighborhood Archetypes and Cardiovascular Health in Black Breast Cancer Survivors.

Background: Maintaining cardiovascular health (CVH) is critical for breast cancer (BC) survivors, particularly given the potential cardiotoxic effects of cancer treatments. Poor CVH among Black BC survivors may be influenced by various area-level social determinants of health, yet the impact of neighborhood archetypes in CVH among this population remains understudied. Objectives: This study aimed to characterize the neighborhood archetypes where Black BC survivors resided at diagnosis and evaluate their associations with CVH. Methods: We assessed CVH 24 months post-diagnosis in 713 participants diagnosed between 2012 and 2017 in the Women's Circle of Health Follow-Up Study, a population-based study of Black BC survivors in New Jersey. Neighborhood archetypes, identified via latent class analysis based on 16 social and built environment features, were categorized into tertiles. Associations between neighborhood archetypes and CVH scores were estimated using polytomous logistic regression. Results: CVH scores were assessed categorically (low, moderate, and optimal) and as continuous variables. On average, Black BC survivors achieved only half of the recommended score for optimal CVH. Among the 4 identified archetypes, women in the Mostly Culturally Black and Hispanic/Mixed Land Use archetype showed the lowest CVH scores. Compared to this archetype, Black BC survivors in the Culturally Diverse/Mixed Land Use archetype were nearly 3 times as likely to have optimal CVH (relative risk ratio: 2.92; 95% CI: 1.58-5.40), with a stronger association observed in younger or premenopausal women. No significant CVH differences were noted for the other 2 archetypes with fewer built environment features. Conclusions: Neighborhood archetypes, integrating social and built environment factors, may represent crucial targets for promoting CVH among BC survivors.

Patterns of B-cell lymphocyte expression changes in pre- and post-malignant prostate tissue are associated with prostate cancer progression.

BACKROUND: Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T- and B-cell levels change during carcinogenesis and whether such changes influence disease progression. METHODS: The study used a retrospective sample of 73 prostate cancer cases (45 whites and 28 African Americans) that underwent surgery as their primary treatment and had a benign prostate biopsy at least 1 year before diagnosis. CD3+, CD4+, and CD20+ lymphocytes were quantified by immunohistochemistry in paired pre- and post-diagnostic benign prostate biopsy and tumor surgical specimens, respectively. Clusters of similar trends of expression across two different timepoints and three distinct prostate regions-benign biopsy glands (BBG), tumor-adjacent benign glands (TAG), and malignant tumor glandular (MTG) regions-were identified using Time-series Anytime Density Peaks Clustering (TADPole). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of time to biochemical recurrence associated with region-specific lymphocyte counts and regional trends. RESULTS: The risk of biochemical recurrence was significantly reduced in men with an elevated CD20+ count in TAG (HR = 0.81, p = 0.01) after adjusting for covariates. Four distinct patterns of expression change across the BBG-TAG-MTG regions were identified for each marker. For CD20+, men with low expression in BBG and higher expression in TAG compared to MTG had an adjusted HR of 3.06 (p = 0.03) compared to the reference group that had nominal differences in CD20+ expression across all three regions. The two CD3+ expression patterns that featured lower CD3+ expression in the BBG compared to the TAG and MTG regions had elevated HRs ranging from 3.03 to 4.82 but did not reach statistical significance. CONCLUSIONS: Longitudinal and spatial expression patterns of both CD3+ and CD20+ suggest that increased expression in benign glands during prostate carcinogenesis is associated with an aggressive disease course.

Robot-Assisted Surgery and Racial and Ethnic Disparities in Post-Prostatectomy Outcomes Among Prostate Cancer Patients.

BACKGROUND: We sought to determine whether the differences in short-term outcomes between patients undergoing robot-assisted radical prostatectomy (RARP) and those treated with open radical prostatectomy (ORP) differ by race and ethnicity. METHODS: This observational study used New York State Cancer Registry data linked to discharge records and included patients undergoing radical prostatectomy for localized prostate cancer during 2008-2018. We used logistic regression to examine the association between race and ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic), surgical approach (RARP, ORP), and postoperative outcomes (major events, prolonged length of stay [pLOS], 30-day re-admission). We tested interaction between race and ethnicity and surgical approach on multiplicative and additive scales. RESULTS: The analytical cohort included 18,926 patients (NHW 14,215 [75.1%], NHB 3195 [16.9%], Hispanic 1516 [8.0%]). The average age was 60.4 years (standard deviation 7.1). NHB and Hispanic patients had lower utilization of RARP and higher risks of postoperative adverse events than NHW patients. NHW, NHB, and Hispanic patients all had reduced risks of adverse events when undergoing RARP versus ORP. The absolute reductions in the risks of major events and pLOS following RARP versus ORP were larger among NHB {relative excess risk due to interaction (RERI): major events -0.32 [95% confidence interval (CI) -0.71 to -0.03]; pLOS -0.63 [95% CI -0.98 to -0.35]) and Hispanic (RERI major events -0.27 [95% CI -0.77 to 0.09]; pLOS -0.93 [95% CI -1.46 to -0.51]) patients than among NHW patients. The interaction was absent on the multiplicative scale. CONCLUSIONS: RARP use has not penetrated and benefited all racial and ethnic groups equally. Increasing utilization of RARP among NHB and Hispanic patients may help reduce disparities in patient outcomes after radical prostatectomy.

Racial and Ethnic Disparities in the Use of Robot-Assisted Surgery and Minimally Invasive Surgery in Pelvic Cancer Treatment: A Systematic Review.

Surgical innovations for cancer treatment may penetrate differentially across racial and ethnic groups and contribute to disparities in health and health care quality. We summarized the current evidence of racial and ethnic disparities in robot-assisted surgery (RAS) and minimally invasive surgery (MIS) use in four major pelvic cancer treatments. We identified studies related to racial and ethnic disparities in RAS and/or MIS use in the treatment of prostate, endometrial, bladder, and rectal cancers during 2001 to 2022 from PubMed, EMBASE, and the Cochrane database. Twenty-eight studies were selected (prostate = 7, endometrial = 14, bladder = 1, rectal = 5, multiple cancers = 1) and all were retrospective. Thirteen and 23 studies examined racial and ethnic differences in individual patients' receipt of RAS and MIS, respectively. Black patients were less likely to receive RAS/MIS than White patients in most studies. Hispanic patients were less likely to receive RAS/MIS than White patients in just over half of the studies. Studies of Asian patients were few and reported mixed results. Three studies examined disparities on the center level and found that racial and ethnic minority prostate cancer patients were less likely to be treated at RAS-performing or high-technology facilities. More work is needed to improve understanding of the mechanisms underlying racial and ethnic disparities in RAS and MIS use and their impact on disparities in health outcomes.

Long-Term Exposure to Walkable Residential Neighborhoods and Risk of Obesity-Related Cancer in the New York University Women's Health Study (NYUWHS).

BACKGROUND: Living in neighborhoods with higher levels of walkability has been associated with a reduced risk of obesity and higher levels of physical activity. Obesity has been linked to increased risk of 13 cancers in women. However, long-term prospective studies of neighborhood walkability and risk for obesity-related cancer are scarce. OBJECTIVES: We evaluated the association between long-term average neighborhood walkability and obesity-related cancer risk in women. METHODS: The New York University Women's Health Study (NYUWHS) is a prospective cohort with 14,274 women recruited between 1985 and 1991 in New York City and followed over nearly three decades. We geocoded residential addresses for each participant throughout follow-up and calculated an average annual measure of neighborhood walkability across years of follow-up using data on population density and accessibility to destinations associated with geocoded residential addresses. We used ICD-9 codes to characterize first primary obesity-related cancers and employed Cox proportional hazards models to assess the association between average neighborhood walkability and risk of overall and site-specific obesity-related cancers. RESULTS: Residing in neighborhoods with a higher walkability level was associated with a reduced risk of overall and site-specific obesity-related cancers. The hazards ratios associated with a 1-standard deviation increase in average annual neighborhood walkability were 0.88 (95% CI: 0.85, 0.93) for overall obesity-related cancer, 0.89 (95% CI: 0.84, 0.95) for postmenopausal breast cancer, 0.82 (95% CI: 0.68, 0.99) for ovarian cancer, 0.87 (95% CI: 0.76, 0.99) for endometrial cancer, and 0.68 (95% CI: 0.49, 0.94) for multiple myeloma, adjusting for potential confounders at both the individual and neighborhood level. The association between neighborhood walkability and risk of overall obesity-related cancer was stronger among women living in neighborhoods with higher levels of poverty compared with women living in areas with lower poverty levels (pInteraction=0.006). DISCUSSION: Our study highlights a potential protective role of neighborhood walkability in preventing obesity-related cancers in women. https://doi.org/10.1289/EHP11538.

Housing instability and psychological distress in African American cancer survivors: findings from the Detroit Research on Cancer Survivors study.

PURPOSE: As health care systems seek to screen for and address housing instability in patient populations, robust evidence linking unstable housing to patient-reported outcomes is needed. Housing instability may increase psychological distress in cancer survivors, potentially more so among African American cancer survivors who are also likely to experience disproportionate burden of housing instability. The purpose of this analysis was to estimate associations between housing instability and psychological distress in African Americans diagnosed with cancer. METHODS: We included survey responses from 2875 African American cancer survivors in the Detroit Research on Cancer Survivors (ROCS) study. We examined how housing instability at enrollment, using an item adapted from the Health Leads Screening Toolkit, related to psychological distress at enrollment, using Patient Reported Outcomes Measurement System (PROMIS) 4-item anxiety and depression short forms. Linear regression models adjusted for sociodemographic factors were used to estimate associations overall and stratified by stage at diagnosis. RESULTS: Approximately 12% of participants reported being unstably housed. Housing instability was associated with significant differences in PROMIS scores for both anxiety (difference: 6.79; 95% CI: 5.57-8.01) and depression (difference: 6.16; 95% CI: 4.99-7.34). We did not find meaningful differences stratifying by disease stage. CONCLUSION: Housing instability was experienced by over a tenth of this cohort of African American cancer survivors and was related to statistically and clinically meaningful differences in psychological distress even following adjustment for sociodemographics. IMPLICATIONS FOR CANCER SURVIVORS: These findings provide evidence supporting screening of housing instability in cancer survivors, especially those from medically underserved populations.

Associations between observed neighborhood physical disorder and health behaviors, New Jersey behavioral risk factor Surveillance System 2011-2016.

This study tested associations between observed neighborhood physical disorder and tobacco use, alcohol binging, and sugar-sweetened beverage consumption among a large population-based sample from an urban area of the United States. Individual-level data of this cross-sectional study were from adult respondents of the New Jersey Behavioral Risk Factor Surveillance System, 2011-2016 (n = 62,476). Zip code tabulation area-level observed neighborhood physical disorder were from virtual audits of 23,276 locations. Tobacco use (current cigarette smoking or chewing tobacco, snuff, or snus use), monthly binge drinking occasions (5+/4+ drinks per occasion among males/females), and monthly sugar-sweetened beverages consumed were self-reported. Logistic and negative binomial regression models were used to generate odds ratios, prevalence rate ratios (PRR), 95 % confidence intervals (CI) by levels of physical disorder. Compared to the lowest quartile, residence in the second (PRR: 1.16; 95 % CI: 1.03, 1.13), third (PRR: 1.24; 95 % CI: 1.10, 1.40), and fourth (highest) quartile of physical disorder (PRR: 1.24; 95 % CI: 1.10, 1.40) was associated with higher monthly sugar-sweetened beverage consumption. Associations involving tobacco use and alcohol binging were mixed. Observed neighborhood disorder might be associated with unhealthy behaviors, especially sugar-sweetened beverage consumption.

Mitochondrial DNA copy number dynamics and associations with the prenatal environment from birth through adolescence in a population of Dominican and African American children.

Mitochondrial DNA copy number (mtDNAcn) dynamics throughout childhood are poorly understood. We profiled mtDNAcn from birth through adolescence and evaluated how the prenatal environment influences mtDNAcn across childhood. Data were collected from children from New York City followed through 18 years. Using duplexed qRT-PCR, we quantified mtDNAcn relative to nuclear DNA in blood collected from the umbilical cord (n = 450), children aged 5-7 (n = 510), and adolescents aged 15-18 (n = 278). We examined mtDNAcn across childhood with linear mixed-effects models (LMM). Relative mtDNAcn was lowest at birth (mean ± SD: 0.67 ± 0.35) and increased in childhood (1.24 ± 0.50) then slightly declined in adolescence (1.13 ± 0.44). We observed no differences in mtDNAcn by sex or race/ethnicity. mtDNAcn was positively associated with prenatal environmental tobacco smoke exposure (0.077 [ 0.01, 0.14] change in relative mtDNAcn) but negatively associated with maternal completion of high school (-0.066 [-0.13, 0.00]), with the receipt of public assistance at birth (-0.074 [-0.14, -0.01]), and when mother born outside the U.S (-0.061 [-0.13, 0.003]). Infant birth outcomes were not associated with mtDNAcn. MtDNAcn levels were dynamic through childhood and associated with some prenatal factors, underscoring the need for the investigation of longitudinal mtDNAcn for human health research.

Neighborhood walkability and sex steroid hormone levels in women.

BACKGROUND: Neighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher concentration of SHBG in women. However, no study has directly examined the association of NW with female sex hormone levels. OBJECTIVE: We conducted a cross-sectional study to evaluate the association between NW and circulating levels of sex hormones and SHBG in pre- and post-menopausal women. METHODS: We included 797 premenopausal and 618 postmenopausal women from the New York University Women's Health Study (NYUWHS) who were healthy controls in previous nested case-control studies in which sex hormones (androstenedione, testosterone, DHEAS, estradiol and estrone) and SHBG had been measured in serum at enrollment. Baseline residential addresses were geo-coded and the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) was calculated. Generalized Estimating Equations were used to assess the association between BEH-NWI and sex hormone and SHBG concentrations adjusting for individual- and neighborhood-level factors. RESULTS: In premenopausal women, a one standard deviation (SD) increment in BEH-NWI was associated with a 3.5% (95% CI 0.9%-6.1%) lower DHEAS concentration. In postmenopausal women, a one SD increment in BEH-NWI was related to an 8.5% (95% CI 5.4%-11.5%) lower level of DHEAS, a 3.7% (95% CI 0.5%-6.8%) lower level of testosterone, a 1.8% (95% CI 0.5%-3.0%) lower level of estrone, and a 4.2% (95% CI 2.7%-5.7%) higher level of SHBG. However, the associations with respect to DHEAS and estrone became apparent only after adjusting for neighborhood-level variables. Sensitivity analyses using fixed effects meta-analysis and inverse probability weighting accounting for potential selection bias yielded similar results. CONCLUSION: Our findings suggest that NW is associated with lower concentrations of androgens and estrone, and increased SHBG, in postmenopausal women, and lower levels of DHEAS in premenopausal women.

Validating a spatio-temporal model of observed neighborhood physical disorder.

This study tested spatio-temporal model prediction accuracy and concurrent validity of observed neighborhood physical disorder collected from virtual audits of Google Street View streetscapes. We predicted physical disorder from spatio-temporal regression Kriging models based on measures at three dates per each of 256 streestscapes (n = 768 data points) across an urban area. We assessed model internal validity through cross validation and external validity through Pearson correlations with respondent-reported perceptions of physical disorder from a breast cancer survivor cohort. We compared validity among full models (both large- and small-scale spatio-temporal trends) versus large-scale only. Full models yielded lower prediction error compared to large-scale only models. Physical disorder predictions were lagged at uniform distances and dates away from the respondent-reported perceptions of physical disorder. Correlations between perceived and observed physical disorder predicted from the full model were higher compared to that of the large-scale only model, but only at locations and times closest to the respondent's exact residential address and questionnaire date. A spatio-temporal Kriging model of observed physical disorder is valid.

Race Differences in Telomere Length in Benign Prostate Biopsies and Subsequent Risk of Prostate Cancer.

BACKGROUND: Telomere shortening is linked to aging and may be associated with increased risk for cancer. Most cancer studies have used telomere length in leukocytes rather than in the target tissue of cancer origin. METHODS: A case-control study of 524 case-control pairs with a benign prostate biopsy nested within a historical cohort of 10,478 men was conducted to determine whether premalignant prostate telomere length (assessed using a modified qRT-PCR) is associated with prostate cancer risk. RESULTS: Telomere lengths in benign prostate biopsies of cases versus controls were similar (1.46 ± 0.38 vs. 1.45 ± 0.42; P = 0.49). African American (AA) men had significantly shorter telomeres compared with White men (1.51 ± 0.38 vs. 1.63 ± 0.39; P < 0.0001). In race-stratified analyses, increasing telomere length was more strongly associated with prostate cancer risk in White men, wherein those with telomere length in the highest quartile had 1.9-fold greater adjusted risk of prostate cancer compared with men with prostate telomere lengths in the lowest quartile [OR = 1.90; 95% confidence interval (CI) = 1.08-3.36]. Men in the highest telomere length quartile also had a greater risk of aggressive prostate cancer compared with men with telomere lengths in the lowest quartile (OR = 2.78; 95% CI = 1.25-6.19). CONCLUSIONS: White men have longer telomeres in benign prostate tissue compared with AA men, and those with the longest telomeres may be at increased risk for prostate cancer, particularly the more aggressive form of the disease. IMPACT: Race-specific telomere length measures may be an early biomarker of aggressive prostate cancer.

Multilevel Factors for Adiposity Change in a Population-Based Prospective Study of Black Breast Cancer Survivors.

PURPOSE: Unfavorable weight change after breast cancer diagnosis increases the risk of mortality, but individual and neighborhood risk factors affecting postdiagnosis weight and body fat changes are unclear among Black women, who have higher rates of obesity and mortality than any other racial/ethnic group. METHODS: Adiposity changes during the period approximately 10 months-24 months after diagnosis were evaluated among 785 women diagnosed between 2012 and 2018 and enrolled in the Women's Circle of Health Follow-Up Study, a population-based prospective cohort of Black breast cancer survivors in New Jersey. Multilevel factors for weight and fat mass change (with gain or loss defined as a relative difference of 3% or more, and considering whether changes were intentional or unintentional) were estimated using multivariable polytomous logistic regressions and multilevel models. RESULTS: Adiposity gain was prevalent: 28% and 47% gained weight and body fat, respectively, despite a high baseline prevalence of overweight or obesity (86%). Risk factors for fat mass gain included receiving chemotherapy (relative risk ratio: 1.59, 95% CI, 1.08 to 2.33) and residing in neighborhoods with a greater density of fast-food restaurants (relative risk ratio comparing highest with lowest tertile: 2.18, 95% CI, 1.38 to 3.46); findings were similar for weight gain. Only 9% of women had intentional weight loss, and multilevel risk factors differed vastly from unintentional loss. CONCLUSION: Both individual and neighborhood factors were associated with adiposity change among Black breast cancer survivors. Residential environment characteristics may offer clinically meaningful information to identify cancer survivors at higher risk for unfavorable weight change and to address barriers to postdiagnosis weight management.

Associations between neighborhood disinvestment and breast cancer outcomes within a populous state registry.

BACKGROUND: Breast cancer (BrCa) outcomes vary by social environmental factors, but the role of built-environment factors is understudied. The authors investigated associations between environmental physical disorder-indicators of residential disrepair and disinvestment-and BrCa tumor prognostic factors (stage at diagnosis, tumor grade, triple-negative [negative for estrogen receptor, progesterone receptor, and HER2 receptor] BrCa) and survival within a large state cancer registry linkage. METHODS: Data on sociodemographic, tumor, and vital status were derived from adult women who had invasive BrCa diagnosed from 2008 to 2017 ascertained from the New Jersey State Cancer Registry. Physical disorder was assessed through virtual neighborhood audits of 23,276 locations across New Jersey, and a personalized measure for the residential address of each woman with BrCa was estimated using universal kriging. Continuous covariates were z scored (mean ± standard deviation [SD], 0 ± 1) to reduce collinearity. Logistic regression models of tumor factors and accelerated failure time models of survival time to BrCa-specific death were built to investigate associations with physical disorder adjusted for covariates (with follow-up through 2019). RESULTS: There were 3637 BrCa-specific deaths among 40,963 women with a median follow-up of 5.3 years. In adjusted models, a 1-SD increase in physical disorder was associated with higher odds of late-stage BrCa (odds ratio, 1.09; 95% confidence interval, 1.02-1.15). Physical disorder was not associated with tumor grade or triple-negative tumors. A 1-SD increase in physical disorder was associated with a 10.5% shorter survival time (95% confidence interval, 6.1%-14.6%) only among women who had early stage BrCa. CONCLUSIONS: Physical disorder is associated with worse tumor prognostic factors and survival among women who have BrCa diagnosed at an early stage.

Pathways between objective and perceived neighborhood factors among Black breast cancer survivors.

BACKGROUND: Mounting evidence supports associations between objective neighborhood disorder, perceived neighborhood disorder, and health, yet alternative explanations involving socioeconomic and neighborhood social cohesion have been understudied. We tested pathways between objective and perceived neighborhood disorder, perceived neighborhood social cohesion, and socioeconomic factors within a longitudinal cohort. METHODS: Demographic and socioeconomic information before diagnosis was obtained at interviews conducted approximately 10 months post-diagnosis from participants in the Women's Circle of Health Follow-up Study - a cohort of breast cancer survivors self-identifying as African American or Black women (n = 310). Neighborhood perceptions were obtained during follow-up interviews conducted approximately 24 months after diagnosis. Objective neighborhood disorder was from 9 items audited across 23,276 locations using Google Street View and scored to estimate disorder values at each participant's residential address at diagnosis. Census tract socioeconomic and demographic composition covariates were from the 2010 U.S. Census and American Community Survey. Pathways to perceived neighborhood disorder were built using structural equation modelling. Model fit was assessed from the comparative fit index and root mean square error approximation and associations were reported as standardized coefficients and 95% confidence intervals. RESULTS: Higher perceived neighborhood disorder was associated with higher objective neighborhood disorder (ß = 0.20, 95% CI: 0.06, 0.33), lower neighborhood social cohesion, and lower individual-level socioeconomic factors (final model root mean square error approximation 0.043 (90% CI: 0.013, 0.068)). Perceived neighborhood social cohesion was associated with individual-level socioeconomic factors and objective neighborhood disorder (ß = - 0.11, 95% CI: - 0.24, 0.02). CONCLUSION: Objective neighborhood disorder might be related to perceived disorder directly and indirectly through perceptions of neighborhood social cohesion.

Neighborhood Walkability and Mortality in a Prospective Cohort of Women.

BACKGROUND: There is a paucity of prospective cohort studies evaluating neighborhood walkability in relation to the risk of death. METHODS: We geocoded baseline residential addresses of 13,832 women in the New York University Women's Health Study (NYUWHS) and estimated the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) for each participant circa 1990. The participants were recruited from 1985 to 1991 in New York City and followed for an average of 27 years. We conducted survival analyses using Cox proportional hazards models to assess the association between neighborhood walkability and risk of death from any cause, obesity-related diseases, cardiometabolic diseases, and obesity-related cancers. RESULTS: Residing in a neighborhood with a higher neighborhood walkability score was associated with a lower mortality rate. Comparing women in the top versus the lowest walkability tertile, the hazards ratios (and 95% CIs) were 0.96 (0.93, 0.99) for all-cause, 0.91 (0.86, 0.97) for obesity-related disease, and 0.72 (0.62, 0.85) for obesity-related cancer mortality, respectively, adjusting for potential confounders at both the individual and neighborhood level. We found no association between neighborhood walkability and risk of death from cardiometabolic diseases. Results were similar in analyses censoring participants who moved during follow-up, using multiple imputation for missing covariates, and using propensity scores matching women with high and low neighborhood walkability on potential confounders. Exploratory analyses indicate that outdoor walking and average BMI mediated the association between neighborhood walkability and mortality. CONCLUSION: Our findings are consistent with a protective role of neighborhood walkability in obesity-related mortality in women, particularly obesity-related cancer mortality.

Neighborhood walkability and body mass index in African American cancer survivors: The Detroit Research on Cancer Survivors study.

BACKGROUND: Extant evidence links neighborhood walkability with obesity-related health in the general population. This association likely exists in cancer survivors, but research is limited. Furthermore, a disproportionate obesity burden in African American cancer survivors warrants subgroup-specific analyses. METHODS: This study analyzed data from 2089 African American cancer survivors participating in the Detroit Research on Cancer Survivors (ROCS) cohort. On the basis of built environment data summarized within 1-km radial buffers around census block centroids, a multidimensional neighborhood walkability index (NWI) was constructed. Survivors' residential addresses at Detroit ROCS enrollment were geocoded, and addresses were linked to NWI scores via the census block of residence. At study enrollment, survivors reported height and weight; these data were used to calculate their body mass index (BMI). Associations between NWI quartiles and BMI overall and by cancer type, biological sex, and physical activity engagement were evaluated. RESULTS: BMI was found to be inversely associated with increasing NWI quartile (P for trend < .01). This inverse relationship was observed in men (P for trend < .01) and in survivors reporting any regular physical activity (P for trend < .01). CONCLUSIONS: This study's findings suggest that among African American cancer survivors, higher neighborhood walkability is associated with lower BMI. As health care systems in the United States increasingly consider the role of the neighborhood environment in their patients' health, these findings provide additional evidence supporting health systems' incorporation of neighborhood walkability as an obesity-related health indicator for this cancer survivor subgroup and potentially for cancer survivors from other vulnerable populations.

Racial differences in the systemic inflammatory response to prostate cancer.

Systemic inflammation may increase risk for prostate cancer progression, but the role it plays in prostate cancer susceptibility is unknown. From a cohort of over 10,000 men who had either a prostate biopsy or transurethral resection that yielded a benign finding, we analyzed 517 incident prostate cancer cases identified during follow-up and 373 controls with one or more white blood cell tests during a follow-up period between one and 18 years. Multilevel, multivariable longitudinal models were fit to two measures of systemic inflammation, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR), to determine NLR and MLR trajectories associated with increased risk for prostate cancer. For both measures, we found no significant differences in the trajectories by case/control status, however in modeling NLR trajectories there was a significant interaction between race (white or Black and case-control status. In race specific models, NLR and MLR values were consistently higher over time among white controls than white cases while case-control differences in NLR and MLR trajectories were not apparent among Black men. When cases were classified as aggressive as compared to non-aggressive, the case-control differences in NLR and MLR values over time among white men were most apparent for non-aggressive cases. For NLR among white men, significant case-control differences were observed for the entire duration of observation for men who had inflammation in their initial prostate specimen. It is possible that, among white men, monitoring of NLR and MLR trajectories after an initial negative biopsy may be useful in monitoring prostate cancer risk.

Growth and differentiation factor 15 and NF-κB expression in benign prostatic biopsies and risk of subsequent prostate cancer detection.

Growth and differentiation factor 15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1), may act as both a tumor suppressor and promotor and, by regulating NF-κB and macrophage signaling, promote early prostate carcinogenesis. To determine whether expression of these two inflammation-related proteins affect prostate cancer susceptibility, dual immunostaining of benign prostate biopsies for GDF-15 and NF-κB was done in a study of 503 case-control pairs matched on date, age, and race, nested within a historical cohort of 10,478 men. GDF-15 and NF-κB expression levels were positively correlated (r = 0.39; p < 0.0001), and both were significantly lower in African American (AA) compared with White men. In adjusted models that included both markers, the odds ratio (OR) for NF-κB expression was statistically significant, OR =0.87; p = 0.03; 95% confidence interval (CI) =0.77-0.99, while GDF-15 expression was associated with a nominally increased risk, OR =1.06; p = 0.27; 95% CI =0.96-1.17. When modeling expression levels by quartiles, the highest quartile of NF-κB expression was associated with almost a fifty percent reduction in prostate cancer risk (OR =0.51; p = 0.03; 95% CI =0.29-0.92). In stratified models, NF-κB had the strongest negative association with prostate cancer in non-aggressive cases (p = 0.03), older men (p = 0.03), and in case-control pairs with longer follow-up (p = 0.02). Risk associated with GDF-15 expression was best fit using nonlinear regression modeling where both first (p = 0.02) and second (p = 0.03) order GDF-15 risk terms were associated with significantly increased risk. This modeling approach also revealed significantly increased risk associated with GDF-15 expression for subsamples defined by AA race, aggressive disease, younger age, and in case-control pairs with longer follow-up. Therefore, although positively correlated in benign prostatic biopsies, NF-κB and GDF-15 expression appear to exert opposite effects on risk of prostate tumor development.

Associations of prenatal exposure to polycyclic aromatic hydrocarbons with pubertal timing and body composition in adolescent girls: Implications for breast cancer risk.

BACKGROUND: While animal data support an association between prenatal exposure to endocrine disrupting chemicals (EDCs) and altered mammary gland development and tumorigenesis, epidemiologic studies have only considered a few classes of EDCs in association with pubertal growth and development in girls. Polycyclic aromatic hydrocarbons (PAH) are a class of EDCs that have not been rigorously evaluated in terms of prenatal exposure and pubertal growth and development in girls. OBJECTIVE: In a New York City birth cohort of Black and Hispanic girls (n = 196; recruited 1998-2006), we examined associations of prenatal PAH exposure with self-reported age at growth spurt onset, breast development onset and menarche, and clinical measures of adolescent body composition including body mass index, waist-to-hip ratio, and body fat measured at ages 11-20 years. METHODS: We measured prenatal exposure to PAH using personal air monitoring data collected from backpacks worn by mothers during the third trimester of pregnancy (data available for all 196 girls) and biomarkers of benzo[α]pyrene-DNA adducts in umbilical cord blood (data available for 106 girls). We examined associations of prenatal PAH with the timing of pubertal milestones and adolescent body composition (11-20 years) using multivariable linear regression models adjusted for race/ethnicity, household public assistance status at birth, and age at outcome assessment. We also fit models further adjusted for potential mediators, including birthweight and childhood body size (BMI-for-age z-score measured at 6-8 years). RESULTS: Girls in the highest versus lowest tertile of ambient exposure to PAH, based on a summary measure of eight carcinogenic higher-molecular weight non-volatile PAH compounds (Σ8 PAH), had a 0.90 year delay in growth spurt onset (95% confidence interval (CI) = 0.25, 1.55; n = 196), a 0.35 year delay in breast development onset (95% CI = -0.26, 0.95; n = 193), and a 0.59 year delay in menarche (95% CI = 0.06, 1.11; n = 191) in models adjusted for race/ethnicity and household public assistance at birth. The statistically significant associations for age at growth spurt onset and menarche were not impacted by adjustment for birthweight or childhood body size. No differences in BMI-for-age z-score, waist-to-hip ratio, or percent body fat were found between girls in the highest versus lowest tertile of ambient Σ8 PAH. Results were similar when we evaluated benzo[α]pyrene-DNA adduct levels. DISCUSSION: Our results suggest that prenatal exposure to PAH might delay pubertal milestones in girls, but findings need to be replicated in other cohorts using prospectively collected data on pubertal outcomes.