ZIP Code to Genomic Code: Neighborhood Disadvantage, Aggressive Breast Cancer Biology, and Breast Cancer Outcomes.

OBJECTIVE: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. BACKGROUND: ND is associated with shorter breast cancer recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. METHODS: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on the protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity [nuclear factor-κB ( NF-kB ), activator protein 1 ( AP-1 )], sympathetic nervous system (SNS) activity [cyclic 3'-5' adenosine monophosphate response element-binding protein ( CREB )], and protective cellular responses [interferon-regulatory factor ( IRF ) and signal transducer and activator of transcription ( STAT )]. To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. RESULTS: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB , activator protein 1, down-regulated IRF , and signal transducer and activator of transcription) and SNS activation (up-regulated CREB ). Increasing subjective ND (eg, threat to safety) was associated with up-regulated NF-kB and CREB and down-regulated IRF . These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. CONCLUSIONS: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

Incidence of Etiology-specific Hepatocellular Carcinoma: Diverging Trends and Significant Heterogeneity by Race and Ethnicity.

BACKGROUND & AIMS: The main causes of hepatocellular carcinoma (HCC) include chronic hepatitis C and B viral infections (HCV, HBV), nonalcoholic fatty liver disease (NAFLD), and alcohol-related disease (ALD). Etiology-specific HCC incidence rates and temporal trends on a population-basis are needed to improve HCC control and prevention. METHODS: All 14,420 HCC cases from the Florida statewide cancer registry were individually linked to data from the hospital discharge agency and the viral hepatitis department to determine the predominant etiology of each case diagnosed during 2010 to 2018. Age-adjusted incidence rates (AAIRs) were used to assess the intersection between etiology and detailed race-ethnicity. Etiology-specific temporal trends based on diagnosis year were assessed using Joinpoint regression. RESULTS: HCV remains the leading cause of HCC among men, but since 2017 NAFLD-HCC is the leading cause among women. HCV-HCC AAIRs are particularly high among U.S.-born minority men, including Puerto Rican (10.9 per 100,000), African American (8.0 per 100,000), and U.S.-born Mexican American men (7.6 per 100,000). NAFLD is more common among all Hispanics and Filipinos and HBV-HCC among Asian and Haitian black men. HCV-HCC surpasses HBV-HCC in Asian women. ALD-HCC is high among specific Hispanic male groups. Population-based HCV-HCC rates experienced a rapid decline since 2015 (-9.6% annually), whereas ALD-HCC (+6.0%) and NAFLD-HCC (+4.3%) are rising (P < .05). CONCLUSIONS: New direct acting anti-viral drugs have impacted rates of HCV-HCC, offsetting important increases in both ALD- and NAFLD-HCC. Hispanics may be a group of concern because of higher rates for ALD- and NAFLD-HCC. HCC etiology varies remarkably and may warrant specific interventions by detailed race-ethnicity.

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.

Investigating Disparities in Hypopharyngeal/Laryngeal Cancer Survival in Florida With Geospatial Mapping Analysis.

OBJECTIVE: Identify predictors of overall survival (OS) after hypopharyngeal/laryngeal cancer in Florida. MATERIAL AND METHODS: We conducted a retrospective cohort study using data from the Florida Cancer Data System (FCDS) on patients diagnosed with hypopharyngeal or laryngeal cancer from 2010-2017. Primary outcome was OS. Hazard ratios (HRs) were estimated from univariable and multivariable Cox regression models for OS. Data was analyzed from November 1, 2022, to June 30, 2023. RESULTS: We analyzed 6771 patients, who were primarily male (81.2%), White non-Hispanic (WNH) (78.2%), publicly insured (70.1%), married (51.8%), and residents of urban counties (73.6%). Black patients were more likely to be younger at diagnosis (38.9%), single (43.4%), to have distant SEER stage disease (25.6%). Median OS were lowest among patients who were uninsured (34 months), with hypopharyngeal site disease (18 months), and a smoking history (current: 34 months, former: 46 months, no smoking: 63 months). Multivariable Cox regression analysis showed worse OS for single/unmarried vs married (HR 1.47 [95%CI: 1.36-1.59], P < .001), history of tobacco use (current: HR 1.62 [95%CI: 1.440-1.817], P < .001; former smokers: (HR 1.28 [95%CI: 1.139-1.437], P < .001) vs no history). Improved OS was observed among White Hispanics (WH) vs WNH (HR .73 [95%CI: .655-.817], P < .001) and women vs men (HR .88 [95%CI: .807-.954], P = .002). Geographical mapping showed that mortality rates were highest in census tracts with low income and education. CONCLUSION: Our findings suggest that sociodemographic and clinical factors impact OS from hypopharyngeal/laryngeal cancer in Florida and vary geographically within the state. These results will help guide future public health interventions.

Does Neighborhood Social Cohesion Influence Participation in Routine Cancer Screening? Findings From a Representative Sample of Adults in South Florida.

BACKGROUND AND OBJECTIVES: Neighborhood social cohesion (NSC) has been associated with a variety of health outcomes, but limited research has examined its impact on behaviors that support cancer control. The purpose of this study was to examine associations between NSC and guideline-concordant breast, cervical and colorectal cancer screening. METHODS: Data are from a cross-sectional survey administered to 716 adults in South Florida from 2019 to 2020. The analytic samples included adults eligible for breast (n = 134), cervical (n = 195), and colorectal cancer (n = 265) screening. NSC was measured using a validated 5-item instrument. Associations between NSC and guideline-concordant screening were examined using multivariable logistic regression. RESULTS: In fully adjusted analyses, the odds of guideline-concordant breast cancer screening increased by 86% for every unit increase in NSC (aOR = 1.86; 95% CI, 1.03-3.36). NSC was not statistically significantly associated with guideline-concordant cervical cancer screening (aOR = 0.86; 95% CI, 0.54-1.38) or colorectal cancer screening (aOR = 1.29; 95% CI, 0.81-2.04). CONCLUSIONS: These findings suggest that NSC supports some screening behaviors, namely, mammography use. To better understand heterogeneous relationships between NSC and utilization of preventive care services such as cancer screening, more research is needed that disaggregates effects by sex, age, race/ethnicity, and socioeconomic status.

Characterization of fire investigators' polyaromatic hydrocarbon exposures using silicone wristbands.

BACKGROUND: Exposures to polyaromatic hydrocarbons (PAHs) contribute to cancer in the fire service. Fire investigators are involved in evaluations of post-fire scenes. In the US, it is estimated that there are up to 9000 fire investigators, compared to approximately 1.1 million total firefighting personnel. This exploratory study contributes initial evidence of PAH exposures sustained by this understudied group using worn silicone passive samplers. OBJECTIVES: Evaluate PAH exposures sustained by fire investigators at post-fire scenes using worn silicone passive samplers. Assess explanatory factors and health risks of PAH exposure at post-fire scenes. METHODS: As part of a cross-sectional study design, silicone wristbands were distributed to 16 North Carolina fire investigators, including eight public, seven private, and one public and private. Wristbands were worn during 46 post-fire scene investigations. Fire investigators completed pre- and post-surveys providing sociodemographic, occupational, and post-fire scene characteristics. Solvent extracts from wristbands were analyzed via gas chromatography-mass spectrometry (GC-MS). Results were used to estimate vapor-phase PAH concentration in the air at post-fire scenes. RESULTS: Fire investigations lasted an average of 148 minutes, standard deviation ± 93 minutes. A significant positive correlation (r=0.455, p<.001) was found between investigation duration and PAH concentrations on wristbands. Significantly greater time-normalized PAH exposures (p=0.039) were observed for investigations of newer post-fire scenes compared to older post-fire scenes. Regulatory airborne PAH exposure limits were exceeded in six investigations, based on exposure to estimated vapor-phase PAH concentrations in the air at post-fire scenes. DISCUSSION: Higher levels of off-gassing and suspended particulates at younger post-fire scenes may explain greater PAH exposure. Weaker correlations are found between wristband PAH concentration and investigation duration at older post-fire scenes, suggesting reduction of off-gassing PAHs over time. Exceedances of regulatory PAH limits indicate a need for protection against vapor-phase contaminants, especially at more recent post-fire scenes.

Opportunities for cancer prevention at syringe services programs: acceptability of HPV self-sampling and vaccination among people who inject drugs.

INTRODUCTION: Despite having a high risk of acquiring sexually transmitted infections, people who inject drugs (PWID) often do not receive recommended HPV screenings due to barriers to healthcare. Guideline-based cervical HPV screening and vaccination can prevent cervical cancer. Low-cost, low-barrier methods for cancer screening and prevention are important for vulnerable communities such as PWID. METHODS: We examined acceptability of HPV self-sampling at a syringe services program (SSP). Participants with a cervix (n = 49) participated in patient education followed by a survey to assess willingness to perform HPV self-sampling versus standard of care. RESULTS: 59% found self-sampling to be acceptable, citing privacy, ease, and quickness. Among those opting for HPV screening delivered by a provider (n = 16), participants cited concerns about adequate sampling (81%) and test accuracy (75%). Notably, only 18% of participants reported complete HPV vaccination. CONCLUSION: Cervical HPV self-sampling was acceptable to PWID. SSP-based efforts to provide preventative health services could place tools for cancer screening into the hands of PWID, a need-to-reach community.

Intersectional disparities in climate vulnerability and cancer risk.

Despite significant progress in the early detection, treatment, and survivorship of cancer in recent decades, cancer disparities continue to plague segments of the US population. Many of these cancer disparities, especially those among historically marginalized racial and ethnic groups and those with lower socioeconomic resources, are caused and perpetuated by social and structural barriers to health. These social and structural barriers, which operate beyond the framework of cancer control, also systematically increase vulnerability to and decrease adaptive capacity for the deleterious effects of anthropogenic climate change. The established and emerging overlap between climate vulnerability and cancer risk presents complex challenges to cancer control, specifically among populations who suffer compounding hazards and intersectional vulnerabilities. By embracing these intersections, we may be able to conceptualize promising new research frameworks and programmatic opportunities that decrease vulnerability to a wide range of climate and health threats to advance health equity.

Point-of-Care Molecular Test for the Detection of 14 High-Risk Genotypes of Human Papillomavirus in a Single Tube.

Cervical cancers constitute a large disease burden in developing countries, with the human papillomavirus (HPV) being responsible for most cervical lesions. Many regions in low-resource countries lack adequate access to sensitive point-of-care (POC) screening tools, preventing timely diagnosis and treatment. To reduce screening barriers, we developed a POC HPV molecular test that detects 14 high-risk HPV types in 30 min in a single assay. We introduced innovations to the underlying amplification (recombinase polymerase amplification) and detection methodologies such as improved probe design, reagent lyophilization, and pipette-less processing to increase sensitivity while enabling minimally trained personnel to conduct reproducible testing. Based on 198 clinically derived samples, we demonstrated a sensitivity of 93% and a specificity of 73% compared to an FDA-approved polymerase chain reaction-based clinical method. Our modified pipette-less simplified assay had a sensitivity of 96% and a specificity of 83%. The application of our assay is intended as a near-patient screening tool with further evaluation by a clinician for confirmation.

Differences in Cervical Cancer Outcomes by Caribbean Nativity in Black and White Women in Florida.

OBJECTIVE: Racial disparities among women with cervical cancer have been reported but are understudied in Caribbean immigrants. The objective of this study is to describe the disparities in clinical presentation and outcomes between Caribbean-born (CB) and US-born (USB) women with cervical cancer by race and nativity. METHODS: An analysis of the Florida Cancer Data Service (FCDS), the statewide cancer registry, was performed to identify women diagnosed with invasive cervical cancer between 1981 and 2016. Women were classified as USB White or Black and CB White or Black. Clinical data were abstracted. Analyses were done using chi square, ANOVA, Kaplan-Meier and Cox proportional hazards models, with significance set at P < .05. RESULTS: 14 932 women were included in the analysis. USB Black women had the lowest mean age at diagnosis, while CB Black women were diagnosed at later stages of disease. USB White women and CB White women had better OS (median OS 70.4 and 71.5 months, respectively) than USB Black and CB Black women (median OS 42.4 and 63.8 months, respectively) (P < .0001). In multivariable analysis, relative to USB Black women, CB Blacks (HR .67, CI .54-.83), and CB White (HR .66, CI .55-.79) had better odds of OS. White race among USB women was not significantly associated with improved survival (P = .087). CONCLUSION: Race alone is not a determinant of cancer mortality in women with cervical cancer. Understanding the impact of nativity on cancer outcomes is crucial to improve health outcomes.

Translational Epidemiology: An Integrative Approach to Determine the Interplay Between Genetic Ancestry and Neighborhood Socioeconomic Status on Triple Negative Breast Cancer.

OBJECTIVE: To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression. BACKGROUND: Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown. METHODS: Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2-), ER+/HER2+, and ER-/HER2+ disease. RESULTS: Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001-1.126, P =0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151-0.781, P =0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: -0.987-1.116, P =0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ 2 =42004914 ( p =3.70×10 -5 ) in patients with TNBC. CONCLUSIONS: In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC.

Structural Racism and Breast Cancer-specific Survival: Impact of Economic and Racial Residential Segregation.

OBJECTIVE: To analyze the effect of economic and racial/ethnic residential segregation on breast cancer-specific survival (BCSS) in South Florida, a diverse metropolitan area that mirrors the projected demographics of many United States regions. SUMMARY BACKGROUND DATA: Despite advances in diagnosis and treatment, racial and economic disparities in BCSS. This study evaluates these disparities through the lens of racial and economic residential segregation, which approximate the impact of structural racism. METHODS: Retrospective cohort study of stage I to IV breast cancer patients treated at our institution from 2005 to 2017. Our exposures include index of concentration at the extremes, a measurement of economic and racial neighborhood segregation, which was computed at the census-tract level using American Community Survey data. The primary outcome was BCSS. RESULTS: Random effects frailty models predicted that patients living in low-income neighborhoods had higher mortality compared to those living in high-income neighborhoods [hazard ratios (HR): 1.56, 95% confidence interval (CI): 1.23-2.00]. Patients living in low-income non-Hispanic Black and Hispanic neighborhoods had higher mortality compared to those living in high-income non-Hispanic White (NHW) neighborhoods (HR: 2.43, 95%CI: 1.72, 3.43) and (HR: 1.99, 95%CI: 1.39, 2.84), after controlling for patient characteristics, respectively. In adjusted race-stratified analysis, NHWs living in low-income non-Hispanic Black neighborhoods had higher mortality compared to NHWs living in high-income NHW neighborhoods (HR: 4.09, 95%CI: 2.34-7.06). CONCLUSIONS: Extreme racial/ethnic and economic segregation were associated with lower BCSS. We add novel insight regarding NHW and Hispanics to a growing body of literature that demonstrate how the ecological effects of structural racism-expressed through poverty and residential segregation-shape cancer survival.

Developing the Florida Academic Cancer Center Alliance Health Disparities Common Measure: The Florida Health and Ancestry Survey.

PURPOSE: Our specific aim was to develop and assess the consensus-based validity of common measures for understanding health behaviors and ancestry in Florida's population subgroups and establish the feasibility of wide-scale implementation of the measures and biospecimen collection within three cancer centers' catchment areas. METHODS: Using the National Cancer Institute's Grid-Enabled Measures web-based platform and an iterative process, we developed the Florida Health and Ancestry Survey (FHAS). We then used three sampling approaches to implement the FHAS: community-engaged, panel respondent, and random digit dialing (RDD). We asked a subset of participants to provide a saliva sample for future validation of subjective ancestry report with DNA-derived ancestry markers. RESULTS: This process supported the FHAS content validity. As an indicator of feasibility, the goals for completed surveys by sampling approach were met for two of the three cancer centers, yielding a total of 1438 completed surveys. The RDD approach produced the most representative sample. The panel sampling approach produced inadequate representation of older individuals and males. The community-engaged approach along with social media recruitment produced extreme underrepresentation only for males. Two of the cancer centers mailed biospecimen kits, whereas one did not due to resource constraints. On average, the community engaged approach was more productive in obtaining returned biospecimen samples (80%) than the panel approach (48%). CONCLUSIONS: We successfully developed and implemented the FHAS as a common measure to show its feasibility for understanding cancer health disparities in Florida. We identified sampling approach successes and challenges to obtaining biospecimens for ancestry research.

A comparative analysis of histologic types of thyroid cancer between career firefighters and other occupational groups in Florida.

BACKGROUND: Florida Firefighters experience a higher risk of thyroid cancer than non-firefighters. This study examines whether the histologic types and tumor stage of thyroid cancer is different among firefighters compared to other occupational groups. METHODS: Eligible cases were firefighters (n = 120) identified in a linkage of Florida Cancer Data System (FCDS) registry records (1981-2014) and Florida State Fire Marshal's Office employment and certification records, and non-firefighters classified into: blue-collar (n = 655), service (n = 834), white-collar (n = 4,893), and other (n = 1,789). Differences in thyroid histologic type (papillary, follicular, and rare/other less common forms of thyroid cancer), tumor stage, and age at diagnosis were evaluated using multinomial logistic regression models comparing blue-collar, service, white-collar, and other occupational groups with firefighters. Univariate odds ratios as well as odds ratios adjusted for age, gender, race, tumor stage, and year of diagnosis (aOR) and 95% confidence intervals (95%CI) were reported. RESULTS: Service (aOR = 4.12; 95%CI: 1.25-13.65), white-collar (aOR = 3.51; 95%CI: 1.08-11.36), and blue-collar (aOR = 4.59; 95%CI: 1.40-15.07) workers had significantly higher odds of being diagnosed with rare histologic types of thyroid cancer vs papillary type compared to firefighters. Service (aOR = 0.42; 95%CI: 0.27-0.66), white-collar (aOR = 0.39; 95%CI: 0.26-0.59), blue-collar (aOR = 0.36; 95%CI: 0.23-0.56), and other (aOR = 0.34; 95%CI: 0.22-0.53) occupational groups have a significantly lower odds of being diagnosed with rare vs papillary type at a younger age (30-49 years) vs 50-69 years compared to firefighters. However, stage at diagnosis was not significantly different among occupational groups. CONCLUSION: Firefighters diagnosed with thyroid cancer experience a higher odds of papillary compared to rare histologic types of thyroid cancer relative to other workers; there is no evidence of an increased odds of late-stage diagnosis in firefighters relative to other worker groups. Firefighters may benefit from routine screening and active surveillance of suspected thyroid tumors especially given the excellent treatment outcomes available for those diagnosed with early-stage papillary thyroid tumors.

Determinants of stage at diagnosis of HPV-related cancer including area deprivation and clinical factors.

BACKGROUND: Collecting social determinants of health in electronic health records is time-consuming. Meanwhile, an Area Deprivation Index (ADI) aggregates sociodemographic information from census data. The objective of this study was to ascertain whether ADI is associated with stage of human papillomavirus (HPV)-related cancer at diagnosis. METHODS: We tested for the association between the stage of HPV-related cancer presentation and ADI as well as the association between stage and the value of each census-based measure using ordered logistic regression, adjusting for age, race and sex. RESULTS: Among 3247 cases of HPV-related cancers presenting to an urban academic medical center, the average age at diagnosis was 57. The average stage at diagnosis was Surveillance, Epidemiology and End Results Stage 3. In the study population, 43% of patients were female and 87% were white. In this study population, there was no association between stage of HPV-related cancer presentation and either aggregate or individual census variables. CONCLUSIONS: These results may reflect insufficient sample size, a lack of socio-demographic diversity in our population, or suggest that simplifying social determinants of health into a single geocoded index is not a reliable surrogate for assessing a patient's risk for HPV-related cancer.

Predicting DNA methylation from genetic data lacking racial diversity using shared classified random effects.

Public genomic repositories are notoriously lacking in racially and ethnically diverse samples. This limits the reaches of exploration and has in fact been one of the driving factors for the initiation of the All of Us project. Our particular focus here is to provide a model-based framework for accurately predicting DNA methylation from genetic data using racially sparse public repository data. Epigenetic alterations are of great interest in cancer research but public repository data is limited in the information it provides. However, genetic data is more plentiful. Our phenotype of interest is cervical cancer in The Cancer Genome Atlas (TCGA) repository. Being able to generate such predictions would nicely complement other work that has generated gene-level predictions of gene expression for normal samples. We develop a new prediction approach which uses shared random effects from a nested error mixed effects regression model. The sharing of random effects allows borrowing of strength across racial groups greatly improving predictive accuracy. Additionally, we show how to further borrow strength by combining data from different cancers in TCGA even though the focus of our predictions is DNA methylation in cervical cancer. We compare our methodology against other popular approaches including the elastic net shrinkage estimator and random forest prediction. Results are very encouraging with the shared classified random effects approach uniformly producing more accurate predictions - overall and for each racial group.

Racial and Ethnic Disparities in Breast Cancer Survival: Emergence of a Clinically Distinct Hispanic Black Population.

OBJECTIVE: To understand the impact of Black race on breast cancer (BC) presentation, treatment, and survival among Hispanics. SUMMARY OF BACKGROUND DATA: It is well-documented that non-Hispanic Blacks (NHB) present with late-stage disease, are less likely to complete treatment, and have worse survival compared to their non-Hispanic White (NHW) counterparts. However, no data evaluates whether this disparity extends to Hispanic Blacks (HB) and Hispanic Whites (HW). Given our location in Miami, gateway to Latin America and the Caribbean, we have the diversity to evaluate BC outcomes in HB and HW. METHODS: Retrospective cohort study of stage I-IV BC patients treated at our institution from 2005-2017. Kaplan-Meier survival curves were generated and compared using the log-rank test. Multivariable survival models were computed using Cox proportional hazards regression. RESULTS: Race/ethnicity distribution of 5951 patients: 28% NHW, 51% HW, 3% HB, and 18% NHB. HB were more economically disadvantaged, had more aggressive disease, and less treatment compliant compared to HW. 5-year OS by race/ethnicity was: 85% NHW, 84.8% HW, 79.4% HB, and 72.7% NHB (P < 0.001). After adjusting for covariates, NHB was an independent predictor of worse OS [hazard ratio:1.25 (95% confidence interval: 1.01-1.52), P < 0.041)]. CONCLUSIONS: In this first comprehensive analysis of HB and HW, HB have worse OS compared to HW, suggesting that race/ethnicity is a complex variable acting as a proxy for tumor and host biology, as well as individual and neighborhood-level factors impacted by structural racism. This study identifies markers of vulnerability associated with Black race and markers of resiliency associated with Hispanic ethnicity to narrow a persistent BC survival gap.

Overcoming disparities: Multidisciplinary breast cancer care at a public safety net hospital.

PURPOSE: Public safety net hospitals (SNH) serve a disparate patient population; however, little is known about long-term oncologic outcomes of patients receiving care at these facilities. This study is the first to examine overall survival (OS) and the initiation of treatment in breast cancer patients treated at a SNH. METHODS: Patients presenting to a SNH with stage I-IV breast cancer from 2005 to 2017 were identified from the local tumor registry. The hospital has a weekly breast tumor board and a multidisciplinary approach to breast cancer care. Kaplan-Meier survival analysis was performed to identify patient, tumor, and treatment characteristics associated with OS. Factors with a p < 0.1 were included in the Cox proportional hazards model. RESULTS: 2709 breast cancer patients were evaluated from 2005 to 2017. The patient demographics, tumor characteristics, and treatments received were analyzed. Five-year OS was 78.4% (93.9%, 87.4%, 70.9%, and 23.5% for stages I, II, III, and IV, respectively). On multivariable analysis, higher stage, age > 70 years, higher grade, and non-Hispanic ethnicity were associated with worse OS. Patients receiving surgery (HR = 0.33, p < 0.0001), chemotherapy (HR = 0.71, p = 0.006), and endocrine therapy (HR = 0.61, p < 0.0001) had better OS compared to those who did not receive these treatments. CONCLUSION: Despite serving a vulnerable minority population that is largely poor, uninsured, and presenting with more advanced disease, OS at our SNH approaches national averages. This novel finding indicates that in the setting of multidisciplinary cancer care and with appropriate initiation of treatment, SNHs can overcome socioeconomic barriers to achieve equitable outcomes in breast cancer care.

HCV testing: Order and completion rates among baby boomers obtaining care from seven health systems in Florida, 2015-2017.

Many U.S. residents infected with hepatitis C virus (HCV) are baby boomers (born 1945-1965), who remain undiagnosed. Past CDC and USPSTF guidelines recommended one-time HCV testing for all baby boomers, with newer guidelines recommending universal screening for all adults. This retrospective cohort study examined electronic medical records for patient visits from 2015 to 2017 within the OneFlorida Data Trust and University of South Florida Health system. We assessed percentages of HCV tests ordered and completed across four age groups (those born before 1945, 1945-1965, 1966-1985, and after 1985). In 2019, we used logistic regression to examine factors associated with HCV test ordering and completion among baby boomers, including age, race, sex, number of primary care visits, HIV status, hepatitis diagnosis, and liver cancer history. All age groups had low rates of HCV test orders. 4.4% of baby boomers had a test ordered in 2015, and 6.7% in 2016. Of those, 94.5% and 89.7% completed testing, respectively. All other races/ethnicities had lower likelihood of testing completion than Whites (Blacks (aOR 0.82, 95%, CI 0.75-0.91); Asians (0.69, 0.52-0.92); Hispanics (0.29, 0.26-0.32)), although test orders were higher for Asians (1.48, 1.37-1.61) and Blacks (1.78, 1.73-1.82). Tests ordered (11.42, 10.94-11.92) and completed (2.25, 1.94-2.60) were more likely among those with hepatitis history. Test orders were more likely for HIV-positive patients (3.68, 3.45-3.93), but completion was less likely (0.67, 0.57-0.78). Interventions are needed to increase testing rates so that HCV infections are treated early, mitigating HCV-related morbidity and mortality, especially related to liver cancer.

Comparing cancer risk estimates using occupational record linkage approaches in male Florida firefighters.

BACKGROUND: Firefighters have an increased risk of cancer, but variations in reported results could be due to differences in occupational case ascertainment. This study compares cancer risk estimates generated by identifying firefighters from their occupational title available in the Florida Cancer Data System (FCDS) versus identification by a linkage method between the FCDS and the Florida State Fire Marshal's Office. METHODS: Florida firefighter employment records (1972-2012; n = 109,009) were linked with FCDS data (1981-2014; ~3.3 million records), identifying 3760 primary cancers in male firefighters. Using the FCDS occupational data field we identified 1831 male cancer cases in those classified as firefighters, first-line supervisors of firefighting and prevention workers, fire inspectors, emergency medical technicians, or paramedics. Age and calendar year-adjusted odds ratios (aOR) and 95% confidence intervals for firefighters versus non-firefighters were calculated for both groups. RESULTS: For skin cancers the risk estimate for FCDS-indentified firefighters was substantially lower than in the employment-record-linked firefighters (aOR = 1.06; 0.87-1.29 vs. 1.54; 1.37-1.73), but for endocrine system cancers it was greater (aOR = 2.36; 1.77-3.14 vs. 2.08; 1.71-2.53). Remaining cancer risk estimates were in the same direction for the two samples except for lymphoma (aOR = 1.10; 0.90-1.34 vs. 0.86; 0.75-0.99). CONCLUSION: Reliance on occupational title in cancer registry records to characterize firefighter cancer risk may result in estimates that are over- or underestimated depending on cancer site. The authors recommend moving toward national linkages between cancer registries and certification or other administrative records, which are a vital resource for firefighter cancer research.