A Proposed Framework and Lexicon for Cancer Prevention.

SUMMARY: Cancer prevention is central to efforts to control the burden of cancer. We propose a new terminology framework to help guide these efforts and promote a key equity principle: "equal care for equal risk."

Race/ethnic associations with comprehensive cancer center access and clinical trial enrollment for acute leukemia.

BACKGROUND: Clinical trial participation at Comprehensive Cancer Centers (CCC) is inequitable for minoritized race/ethnic groups with acute leukemia. CCCs care for a high proportion of adults with acute leukemia. It is unclear if participation inequities are due to CCC access, post-access enrollment, or both. METHODS: We conducted a retrospective cohort study of adults with acute leukemia (2010-2019) residing within Massachusetts, the designated catchment area of the Dana-Farber/Harvard Cancer Center (DF/HCC). Individuals were categorized as non-Hispanic Asian (NHA), Black (NHB), White (NHW), Hispanic White (HW), or Other. Decomposition analyses assessed covariate contributions to disparities in (1) access to DF/HCC care and (2) post-access enrollment. RESULTS: Of 3698 individuals with acute leukemia, 85.9% were NHW, 4.5% HW, 4.3% NHB, 3.7% NHA, and 1.3% Other. Access was lower for HW (age- and sex-adjusted OR 0.64 95%CI 0.45,0.90) and reduced post-access enrollment for HW (aOR 0.54 95%CI 0.34,0.86) and NHB (aOR 0.60 95%CI 0.39,0.92) compared to NHW. Payor and socioeconomic status (SES) accounted for 25.2% and 21.2% of the +1.1% absolute difference in HW access. Marital status and SES accounted for 8.0% and 7.0% of the -8.8% absolute disparity in HW enrollment; 76.4% of the disparity was unexplained. SES and marital status accounted for 8.2% and 7.1% of the -9.1% absolute disparity in NHB enrollment; 73.0% of the disparity was unexplained. CONCLUSIONS: A substantial proportion of race/ethnic inequities in acute leukemia trial enrollment at CCCs are from post-access enrollment, the majority of which was not explained by sociodemographic factors.

Neighborhood Deprivation, Race and Ethnicity, and Prostate Cancer Outcomes Across California Health Care Systems.

Importance: Non-Hispanic Black (hereafter, Black) individuals experience worse prostate cancer outcomes due to socioeconomic and racial inequities of access to care. Few studies have empirically evaluated these disparities across different health care systems. Objective: To describe the racial and ethnic and neighborhood socioeconomic status (nSES) disparities among residents of the same communities who receive prostate cancer care in the US Department of Veterans Affairs (VA) health care system vs other settings. Design, Setting, and Participants: This cohort study obtained data from the VA Central Cancer Registry for veterans with prostate cancer who received care within the VA Greater Los Angeles Healthcare System (VA cohort) and from the California Cancer Registry (CCR) for nonveterans who received care outside the VA setting (CCR cohort). The cohorts consisted of all males with incident prostate cancer who were living within the same US Census tracts. These individuals received care between 2000 and 2018 and were followed up until death from any cause or censoring on December 31, 2018. Data analyses were conducted between September 2022 and December 2023. Exposures: Health care setting, self-identified race and ethnicity (SIRE), and nSES. Main Outcomes and Measures: The primary outcome was all-cause mortality (ACM). Cox proportional hazards regression models were used to estimate hazard ratios for associations of SIRE and nSES with prostate cancer outcomes in the VA and CCR cohorts. Results: Included in the analysis were 49 461 males with prostate cancer. Of these, 1881 males were in the VA cohort (mean [SD] age, 65.3 [7.7] years; 833 Black individuals [44.3%], 694 non-Hispanic White [hereafter, White] individuals [36.9%], and 354 individuals [18.8%] of other or unknown race). A total of 47 580 individuals were in the CCR cohort (mean [SD] age, 67.0 [9.6] years; 8183 Black individuals [17.2%], 26 206 White individuals [55.1%], and 13 191 individuals [27.8%] of other or unknown race). In the VA cohort, there were no racial disparities observed for metastasis, ACM, or prostate cancer-specific mortality (PCSM). However, in the CCR cohort, the racial disparities were observed for metastasis (adjusted odds ratio [AOR], 1.36; 95% CI, 1.22-1.52), ACM (adjusted hazard ratio [AHR], 1.13; 95% CI, 1.04-1.24), and PCSM (AHR, 1.15; 95% CI, 1.05-1.25). Heterogeneity was observed for the racial disparity in ACM in the VA vs CCR cohorts (AHR, 0.90 [95% CI, 0.76-1.06] vs 1.13 [95% CI, 1.04-1.24]; P = .01). No evidence of nSES disparities was observed for any prostate cancer outcomes in the VA cohort. However, in the CCR cohort, heterogeneity was observed for nSES disparities with ACM (AHR, 0.82; 95% CI, 0.80-0.84; P = .002) and PCSM (AHR, 0.86; 95% CI, 0.82-0.89; P = .007). Conclusions and Relevance: Results of this study suggest that racial and nSES disparities were wider among patients seeking care outside of the VA health care system. Health systems-related interventions that address access barriers may mitigate racial and socioeconomic disparities in prostate cancer.

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men.

Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male pattern baldness comes from individuals of European descent. Here, we examined a novel dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using a custom array. We first tested how genetic predictions of baldness generalize from Europe to Africa, finding that polygenic scores from European GWAS yielded AUC statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness in African populations performed notably worse than in European populations. Subsequently, we conducted the first African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for present age, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p-value < 10-5, r2 < 0.2). Most baldness associations were autosomal, and the X chromosomes does not appear to have a large impact on baldness in African men. Finally, we examined the evolutionary causes of continental differences in genetic architecture. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, we did not find evidence that European-ascertained baldness hits were enriched for signatures of ancient introgression. Most loci that are associated with androgenetic alopecia are evolving neutrally. However, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how evolutionary history contributes to the limited portability of genetic predictions across ancestries.

Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population.

ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. In total, 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE trial). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations of ≥0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared with normal weight (body mass index [BMI] of 18.5 to <25 kg/m2), obesity (BMI of ≥30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.21-2.47; P = .003). High physical activity (≥73.5 metabolic equivalent of task (MET)-hours per week vs <10.5 MET-hours per week) had a decreased likelihood of MS-MGUS (OR, 0.45, 95% CI, 0.24-0.80; P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs never smoker: OR, 2.19; 95% CI, 1.24-3.74; P = .005, and sleep <6 vs ≥6 hours per day: OR, 2.11; 95% CI, 1.26-3.42; P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations of <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified. This trial was registered at www.clinicaltrials.gov as #NCT03689595.

The role of community outreach and engagement in evaluation of NCI Cancer Center Support Grants.

PURPOSE: National Cancer Institute (NCI)-designated cancer centers are required to consider their impact on the catchment area they serve. These activities are facilitated by community outreach and engagement (COE) activities as specified in the Cancer Center Support Grant (CCSG) request for applications. While the critical importance of COE activities to NCI-designated cancer centers is well known, it is less clear what impact the COE component has on the overall CCSG merit descriptor and score. METHODS: We undertook an online survey of all 62 NCI-designated Comprehensive and Clinical centers who reported their COE merit descriptor and overall CCSG priority score as of Fall 2021. RESULTS: Of 48 (77%) of responding centers, we identified a strong correlation between the COE merit descriptor and the overall numerical CCSG score received by the center (Spearman's rank correlation coefficient r = 0.360, p = 0.0053). When stratifying this relationship by center type, we observed a very strong correlation between COE and CCSG ratings for comprehensive cancer centers (n = 40; r = 0.544; p = 0.0003) but not for non-comprehensive cancer centers (n = 8; r = 0.073; p = 0.864). CONCLUSION: COE component merit descriptors for comprehensive cancer center CCSG evaluations are strongly correlated with the overall cancer center review score.

Prostate cancer screening in African American men: a review of the evidence.

BACKGROUND: Prostate cancer is the most diagnosed cancer in African American men, yet prostate cancer screening regimens in this group are poorly guided by existing evidence, given underrepresentation of African American men in prostate cancer screening trials. It is critical to optimize prostate cancer screening and early detection in this high-risk group because underdiagnosis may lead to later-stage cancers at diagnosis and higher mortality while overdiagnosis may lead to unnecessary treatment. METHODS: We performed a review of the literature related to prostate cancer screening and early detection specific to African American men to summarize the existing evidence available to guide health-care practice. RESULTS: Limited evidence from observational and modeling studies suggests that African American men should be screened for prostate cancer. Consideration should be given to initiating screening of African American men at younger ages (eg, 45-50 years) and at more frequent intervals relative to other racial groups in the United States. Screening intervals can be optimized by using a baseline prostate-specific antigen measurement in midlife. Finally, no evidence has indicated that African American men would benefit from screening beyond 75 years of age; in fact, this group may experience higher rates of overdiagnosis at older ages. CONCLUSIONS: The evidence base for prostate cancer screening in African American men is limited by the lack of large, randomized studies. Our literature search supported the need for African American men to be screened for prostate cancer, for initiating screening at younger ages (45-50 years), and perhaps screening at more frequent intervals relative to men of other racial groups in the United States.

Global viewpoints: updates on prostate cancer in Sub-Saharan Africa.

Prostate cancer (PCa) is a major health concern in Sub-Saharan Africa (SSA), with high incidence and mortality rates. However, the widely used prostate-specific antigen (PSA) screening is not readily available or affordable in SSA. Alternative screening strategies, such as risk stratification approaches and cost-effective PSA tests, are being explored to target high-risk individuals and improve access to screening. Diagnosis of PCa in SSA is challenging due to the lack of access to diagnostic tools and limited healthcare resources. Clinical evaluation and digital rectal examination are commonly used, but PSA testing, magnetic resonance imaging, and biopsy are often limited. As a result, many men in SSA are diagnosed at advanced stages of the disease. Treatment options for PCa in SSA are often limited by a lack of resources and trained healthcare providers. Surgery, radiation therapy, and androgen-deprivation therapy are available but may be inaccessible to many patients. Cultural beliefs and stigma surrounding PCa further impact treatment decisions. Improved patient and community awareness, electronic medical records, and communication between patients and healthcare professionals can enhance evidence-based decision-making and advocate for policy changes. Understanding the genetic determinants and implementing comprehensive strategies can lead to improved outcomes and better control of PCa in SSA.

Associations Between Neighborhood-Level Income and Triple-Negative Breast Cancer in a Majority-Minority Population.

BACKGROUND: Previous studies on disparities in triple-negative breast cancer (TNBC) focus on race/ethnicity, with few exploring the impact of contextual factors such as neighborhood-level income. This study evaluates the effect of neighborhood-level income on disparities in TNBC among a racially and ethnically diverse cohort, after accounting for granular individual-level risk factors of TNBC. PATIENTS AND METHODS: Patients with stage I-IV breast cancer from 2005 to 2017 were identified from our local tumor registry. The primary outcome was diagnosis of TNBC. Using 5-years estimates from the American Community Survey, we obtained median household income for each census tract which was categorized into quartiles. Mixed effects logistic regression was conducted and stratified by race and ethnicity, controlling for individual-level sociodemographic, comorbidities, and tumor characteristics. RESULTS: Among 5377 breast cancer registry patients, 16.5% were diagnosed with TNBC. The majority were Hispanic (50.1%) followed by non-Hispanic Black (NHB) (28.0%). After controlling for individual-level covariables including race and ethnicity, comorbidities, and tumor characteristics, women from low-income neighborhoods had increased odds of TNBC compared with other breast cancer subtypes, compared with those in high-income neighborhoods [odds ratio (OR) 1.33; 95% confidence interval (CI) 1.04, 1.70, p < 0.001]. In stratified analyses, NHB patients from low-income neighborhoods had two times the odds of TNBC diagnosis compared with those from high-income neighborhoods (OR 2.11; 95% CI 1.02, 4.37). CONCLUSION: We found that living in a low-income neighborhood is associated with an increased odds of TNBC independent of granular individual-level TNBC risk factors, particularly NHB race. More striking, NHB living in low-income neighborhoods had increased odds of TNBC compared with NHB living in high-income neighborhoods. Our results suggest potential unaccounted gene-environment and/or social (api)genomic interactions between neighborhood-level income and TNBC subtype development.

Prostate-specific antigen testing rates in high-risk populations: results from the All of Us Research Program.

BACKGROUND: Early detection of prostate cancer using prostate-specific antigen (PSA) remains controversial and disparities in the receipt of prostate cancer screening persist in the US. We sought to examine disparities in PSA testing rates among groups with higher prostate cancer risk and differential access to healthcare. METHODS: We identified a cohort of 37,706 males within the All of Us Research Program without a history of prostate cancer between the ages of 40 and 85 at time of enrollment (2017-2021). Incidence rate ratios (IRR) for the number of PSA tests received during follow-up through December 2021 were estimated using age- and multivariable-adjusted negative binomial regression models. PSA testing frequencies in the cohort were compared with population-based estimates from the 2020 Behavioral Risk Factor Surveillance System (BRFSS). RESULTS: A total of 6,486 males (17.2%) received at least one PSA test over the course of follow-up. In multivariable-adjusted models, non-Hispanic Black males received PSA tests at a 17% lower rate (IRR = 0.83, 95% CI 0.76, 0.90) than non-Hispanic White males. Higher educational attainment, higher annual income, having self-/employer-purchased insurance, having a spouse or domestic partner, and having a family history of prostate cancer were all associated with higher rates of PSA testing. The proportion of males ages 55 to 69 who received a PSA test within two years was lower in All of Us (12.4%, 95% CI 11.8-13.0%) relative to population-based estimates from the BRFSS (35.2%, 95% CI 34.2-36.3%). CONCLUSION: Absolute PSA testing rates in All of Us were lower than population-based estimates, but associations with PSA testing in the cohort mirrored previously reported disparities in prostate cancer screening. These findings highlight the importance of addressing barriers to care in order to reduce disparities in cancer screening.

Biochemical progression free and overall survival among Black men with stage IV prostate cancer in South Africa: Results from a prospective cohort study.

BACKGROUND: Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first-line treatment for stage IV PCa. OBJECTIVE: To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT. DESIGN, SETTING, AND PARTICIPANTS: Men diagnosed with prostate cancer (3/22/2016-10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate-specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start. OUTCOMES MEASURES AND STATISTICAL ANALYSIS: We used Kaplan-Meier statistics to estimate OS and Cox regression models to identify predictors of OS. RESULTS AND LIMITATIONS: Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64-73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%-noncalculable), while biochemical progression-free survival was 2.36 years (95% CI: 2.03%-3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%-6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%-7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%-5.83%), and hemoglobin at diagnosis <13.5 g/dL (HR 2.90, 95% CI: 1.28%-6.56%) were associated with worse OS. CONCLUSIONS: In this study, we identified factors associated with poor OS among Black South African men with stage IV PCa treated with ADT. These factors may be useful in identifying patients for upfront treatment escalation, including the use of docetaxel chemotherapy or escalation of therapy at the time of biochemical progression. PATIENT SUMMARY: In this study, we found that high alkaline phosphatase level, anemia at diagnosis, and high PSA nadir after initiation of androgen deprivation therapy are associated with worse overall survival among Black South African men treated with androgen deprivation therapy for metastatic prostate cancer.

Advancing Social and Environmental Research in Cancer Registries Using Geomasking for Address-Level Data.

Understanding the social and environmental causes of cancer in the United States, particularly in marginalized communities, is a major research priority. Population-based cancer registries are essential for advancing this research, given their nearly complete capture of incident cases within their catchment areas. Most registries limit the release of address-level geocodes linked to cancer outcomes to comply with state health departmental regulations. These policies ensure patient privacy, uphold data confidentiality, and enhance trust in research. However, these restrictions also limit the conduct of high-quality epidemiologic studies on social and environmental factors that may contribute to cancer burden. Geomasking refers to computational algorithms that distort locational data to attain a balance between effectively "masking" the original address location while faithfully maintaining the spatial structure in the data. We propose that the systematic deployment of scalable geomasking algorithms could accelerate research on social and environmental contributions across the cancer continuum by reducing measurement error bias while also protecting privacy. We encourage multidisciplinary teams of registry officials, geospatial analysts, cancer researchers, and others engaged in this form of research to evaluate and apply geomasking procedures based on feasibility of implementation, accuracy, and privacy protection to accelerate population-based research on social and environmental causes of cancer.

Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction.

We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.

Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Translational Epidemiology: Genetic Ancestry in Breast Cancer: What Is the Role of Genetic Ancestry and Socioeconomic Status in Triple-Negative Breast Cancer?

Racial/ethnic and socioeconomic disparities seen in triple-negative breast cancer (TNBC) have prompted questions regarding the role of genetic ancestry in breast cancer (BC) subtype development, tumor biology, and ultimately prognosis. The causes of disparities in TNBC are influenced greatly by both sociopolitical factors and genetic ancestry, and now, the potential genomic underpinnings of social factors. To comprehensively understand disparities in TNBC, it is critical to take a translational epidemiologic approach that takes into account genomic and non-genomic factors. Understanding the interplay between genetic ancestry and social genomics and their proportional influence on outcomes can guide our priorities for screening, diagnosis, and interventions for this aggressive BC subtype.

Disparities in Travel-Related Barriers to Accessing Health Care From the 2017 National Household Travel Survey.

Importance: Geographic access, including mode of transportation, to health care facilities remains understudied. Objective: To identify sociodemographic factors associated with public vs private transportation use to access health care and identify the respondent, trip, and community factors associated with longer distance and time traveled for health care visits. Design, Setting, and Participants: This cross-sectional study used data from the 2017 National Household Travel Survey, including 16 760 trips or a nationally weighted estimate of 5 550 527 364 trips to seek care in the United States. Households that completed the recruitment and retrieval survey for all members aged 5 years and older were included. Data were analyzed between June and August 2022. Exposures: Mode of transportation (private vs public transportation) used to seek care. Main Outcomes and Measures: Survey-weighted multivariable logistic regression models were used to identify factors associated with public vs private transportation and self-reported distance and travel time. Then, for each income category, an interaction term of race and ethnicity with type of transportation was used to estimate the specific increase in travel burden associated with using public transportation compared a private vehicle for each race category. Results: The sample included 12 092 households and 15 063 respondents (8500 respondents [56.4%] aged 51-75 years; 8930 [59.3%] females) who had trips for medical care, of whom 1028 respondents (6.9%) were Hispanic, 1164 respondents (7.8%) were non-Hispanic Black, and 11 957 respondents (79.7%) were non-Hispanic White. Factors associated with public transportation use included non-Hispanic Black race (compared with non-Hispanic White: adjusted odds ratio [aOR], 3.54 [95% CI, 1.90-6.61]; P < .001) and household income less than $25 000 (compared with ≥$100 000: aOR, 7.16 [95% CI, 3.50-14.68]; P < .001). The additional travel time associated with use of public transportation compared with private vehicle use varied by race and household income, with non-Hispanic Black respondents with income of $25 000 to $49 999 experiencing higher burden associated with public transportation (mean difference, 81.9 [95% CI, 48.5-115.3] minutes) than non-Hispanic White respondents with similar income (mean difference, 25.5 [95% CI, 17.5-33.5] minutes; P < .001). Conclusions and Relevance: These findings suggest that certain racial, ethnic, and socioeconomically disadvantaged populations rely on public transportation to seek health care and that reducing delays associated with public transportation could improve care for these patients.

Understanding inequities in precision oncology diagnostics.

Advances in molecular diagnostics have enabled the identification of targetable driver pathogenic variants, forming the basis of precision oncology care. However, the adoption of new technologies, such as next-generation sequencing (NGS) panels, can exacerbate healthcare disparities. Here, we summarize data on use patterns of advanced biomarker testing, highlight the disparities in both accessing NGS testing and using this data to match patients to appropriate personalized therapies and propose multidisciplinary strategies to address inequities looking forward.

Associations between Etiologic or Prognostic Tumor Tissue Markers and Neighborhood Contextual Factors in Male Health Professionals Diagnosed with Prostate Cancer.

BACKGROUND: There is growing evidence that unfavorable neighborhood contexts may influence prostate cancer progression. Whether these associations may be explained in part by differences in tumor-level somatic alterations remain unclear. METHODS: Data on tumor markers (PTEN, p53, ERG, and SPINK1) were obtained from 1,157 participants with prostate cancer in the Health Professionals Follow-up Study. Neighborhood greenness, socioeconomic status, and the income Index of Concentration at Extremes were obtained from satellite and census data and linked to participants' address at diagnosis and at study enrollment. Exposures were scaled to an interquartile range and modeled as tertiles. Bivariate associations between tertiles of neighborhood factors and tumor markers were assessed in covariate adjusted logistic regression models to estimate ORs and 95% confidence intervals. RESULTS: There was no association between any of the neighborhood contextual factors and PTEN, p53, ERG, or SPINK1 in bivariate or multivariable adjusted models. Results were generally consistent when modeling exposure using exposure at diagnosis or at study enrollment. CONCLUSIONS: In this multilevel study of men with prostate cancer, we found no evidence of associations between neighborhood context and tumor tissue markers. IMPACT: Our results provide some of the first empirical data in support of the hypothesis that prostate cancer risk conferred by tumor tissue markers may arise independently of underlying neighborhood context. Prospective studies in more diverse populations are needed to confirm these findings.

Influence of Neighborhood Social and Natural Environment on Prostate Tumor Histology in a Cohort of Male Health Professionals.

Adverse neighborhood social and natural (green space) environments may contribute to the etiology of prostate cancer (CaP), but mechanisms are unclear. We examined associations between neighborhood environment and prostate intratumoral inflammation in 967 men diagnosed with CaP with available tissue samples from 1986-2009 in the Health Professionals Follow-up Study. Exposures were linked to work or residential addresses in 1988. We estimated indices of neighborhood socioeconomic status (nSES) and segregation (Index of Concentration at the Extremes (ICE)) using US Census tract-level data. Surrounding greenness was estimated using seasonal averaged Normalized Difference Vegetation Index (NDVI) data. Surgical tissue underwent pathological review for acute and chronic inflammation, corpora amylacea, and focal atrophic lesions. Adjusted odds ratios (aORs) for inflammation (ordinal) and focal atrophy (binary) were estimated using logistic regression. No associations were observed for acute or chronic inflammation. Each interquartile-range increase in NDVI within 1,230 m of the participant's work or home address (aOR = 0.74, 95% confidence interval (CI): 0.59, 0.93), in ICE-income (aOR = 0.79, 95% CI: 0.61, 1.04), and in ICE-race/income (aOR = 0.79, 95% CI: 0.63, 0.99) was associated with lower odds of postatrophic hyperplasia. Interquartile-range increases in nSES (aOR = 0.76, 95% CI: 0.57, 1.02) and ICE-race/income (aOR = 0.73, 95% CI: 0.54, 0.99) were associated with lower odds of tumor corpora amylacea. Histopathological inflammatory features of prostate tumors may be influenced by neighborhood.