Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment and survival in Arizona.

BACKGROUND: Hispanics and American Indians (AI) have high kidney cancer incidence and mortality rates in Arizona. This study assessed: (1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability index (SVI) experience a longer time to surgery after clinical diagnosis, and (2) whether time to surgery, race and ethnicity, and SVI are associated with upstaging to pT3/pT4, disease-free survival (DFS), and overall survival (OS). METHODS: Arizona Cancer Registry (2009-2018) kidney and renal pelvis cases (n = 4592) were analyzed using logistic regression models to assess longer time to surgery and upstaging. Cox-regression hazard models were used to test DFS and OS. RESULTS: Hispanic and AI patients with T1 tumors had a longer time to surgery than non-Hispanic White patients (median time of 56, 55, and 45 days, respectively). Living in neighborhoods with high (≥75) overall SVI increased odds of a longer time to surgery for cT1a (OR 1.54, 95% CI: 1.02-2.31) and cT2 (OR 2.32, 95% CI: 1.13-4.73). Race and ethnicity were not associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3/pT4 (OR 1.95, 95% CI: 0.99-3.84). A longer time to surgery was associated with PFS (HR 1.52, 95% CI: 1.17-1.99) and OS (HR 1.63, 95% CI: 1.26-2.11). Among patients with cT2 tumor, living in high SVI neighborhoods was associated with worse OS (HR 1.66, 95% CI: 1.07-2.57). CONCLUSIONS: High social vulnerability was associated with increased time to surgery and poor survival after surgery.

Derivation and external validation of a risk score for clinically important declines in health and function among two longitudinal cohorts of women in the mid-life.

OBJECTIVES: Women in mid-life often develop chronic conditions and experience declines in physical health and function. Identifying factors associated with declines provides opportunity for targeted interventions. We derived and externally validated a risk score for clinically important declines over 10 years among women ages 55-65 using the Physical Component Summary Score (PCS) of the SF-36. DESIGN: Derivation and validation of a risk score. SETTING: Two longitudinal cohorts from sites in the USA were used. PARTICIPANTS: Women from the Study of Women's Health Across the Nation (SWAN) and women from the Women's Health Initiative (WHI) Observational Study and/or clinical trials. OUTCOME MEASURES: A clinically important decline over 10 years among women ages 55-65 using the PCS of the SF-36 predictors was measured at the beginning of the 10 years of follow-up. RESULTS: Seven factors-lower educational attainment, smoking, higher body mass index, history of cardiovascular disease, history of osteoarthritis, depressive symptoms and baseline PCS level-were found to be significant predictors of PCS decline among women in SWAN with an area under the curve (AUC)=0.71 and a Brier Score=0.14. The same factors were associated with a decline in PCS in WHI with an AUC=0.64 and a Brier Score=0.18. Regression coefficients from the SWAN analysis were used to estimate risk scores for PCS decline in both cohorts. Using a threshold of a 30% probability of a significant decline, the risk score created a binary test with a specificity between 89%-93% and an accuracy of 73%-79%. CONCLUSIONS: Seven clinical variables were used to create a valid risk score for PCS declines that was replicated in an external cohort. The risk score provides a method for identifying women at high risk for a significant mid-life PCS decline.

DNA methylation accelerated age as captured by epigenetic clocks influences breast cancer risk.

Introduction: Breast cancer continues to be the leading form of cancer among women in the United States. Additionally, disparities across the breast cancer continuum continue to increase for women of historically marginalized populations. The mechanism driving these trends are unclear, however, accelerated biological age may provide key insights into better understanding these disease patterns. Accelerated age measured by DNA methylation using epigenetic clocks is to date the most robust method for estimating accelerated age. Here we synthesize the existing evidence on epigenetic clocks measurement of DNA methylation based accelerated age and breast cancer outcomes. Methods: Our database searches were conducted from January 2022 to April 2022 and yielded a total of 2,908 articles for consideration. We implemented methods derived from guidance of the PROSPERO Scoping Review Protocol to assess articles in the PubMed database on epigenetic clocks and breast cancer risk. Results: Five articles were deemed appropriate for inclusion in this review. Ten epigenetic clocks were used across the five articles demonstrating statistically significant results for breast cancer risk. DNA methylation accelerated age varied by sample type. The studies did not consider social factors or epidemiological risk factors. The studies lacked representation of ancestrally diverse populations. Discussion: DNA methylation based accelerated age as captured by epigenetic clocks has a statistically significant associative relationship with breast cancer risk, however, important social factors that contribute to patterns of methylation were not comprehensively considered in the available literature. More research is needed on DNA methylation based accelerated age across the lifespan including during menopausal transition and in diverse populations. This review demonstrates that DNA methylation accelerated age may provide key insights for tackling increasing rates of U.S. breast cancer incidence and overall disease disparities experienced by women from minoritized backgrounds.

Physical Activity in Young BRCA Carriers and Reduced Risk of Breast Cancer.

INTRODUCTION: A systematic literature review was conducted to determine whether physical activity levels during adolescent and young adult years were associated with a reduced lifetime risk of breast cancer among carriers of deleterious mutations in BRCA1 and BRCA2 genes. METHODS: Ovid/MEDLINE, Embase, CENTRAL, WOS, and CINAHL were searched for articles including information about adolescent and young adult physical activity and breast cancer incidence among women carrying deleterious BRCA1 and BRCA2 gene mutations (search was initiated in October 2019; last update and full analyses were in March 2021). Independent reviewers screened articles at the title/abstract and full-text levels, resolving differences by consensus with lead authors. The NIH Quality Assessment Tools were used to assess sources of bias. RESULTS: A total of 1,957 unique articles were identified; 5 met inclusion criteria. Samples size ranged from 68 to 1,185. All studies relied on self-reported adolescent and young adult physical activity. One study measured sports involvement; the others measured recreational activity. One large study was null, whereas 4 others showed a reduction in breast cancer incidence later in life with higher adolescent and young adult physical activity (p≤0.05). However, the protection was limited to premenopausal breast cancer in 1 of the studies (OR=0.62; 95% CI=0.40, 0.96; p-trend=0.01). In addition, adolescent and young adult physical activity was associated with older age at breast cancer diagnosis in 1 study (p=0.03). CONCLUSIONS: A limited number of studies suggest that adolescent and young adult physical activity may reduce or delay the risk of breast cancer incidence among carriers of deleterious mutations in BRCA1 and BRCA2 genes.

Diet-Driven Inflammation and Insulinemia and Risk of Interval Breast Cancer.

Interval breast cancers (IBCs) emerge after a non-suspicious mammogram and before the patient's next scheduled screen. Risk factors associated with IBC have not been identified. This study evaluated if the empirical dietary inflammatory pattern (EDIP) or empirical dietary index for hyperinsulinemia (EDIH) scores are associated with IBC compared to screen-detected breast cancer. Data were from women 50-79 years-old in the Women's Health Initiative cohort who completed food frequency questionnaires at baseline (1993-98) and were followed through March 31, 2019 for breast cancer detection. Women were identified as having either IBC diagnosed within 1-year after their last negative screening mammogram (N = 317) or screen-detected breast cancer (N = 1,928). Multivariable-adjusted logistic regression analyses were used to estimate odds ratios for risk of IBC compared to screen-detected cancer in dietary index tertiles. No associations were observed between EDIP or EDIH and IBC. Odds ratios comparing the highest to the lowest dietary index tertile were 1.08; 95%CI, 0.78-1.48 for EDIP and 0.92; 95%CI, 0.67-1.27 for EDIH. The null associations persisted when stratified by BMI categories. Findings suggest that diet-driven inflammation or insulinemia may not be substantially associated with IBC risk among postmenopausal women. Future studies are warranted to identify modifiable factors for IBC prevention.

Renal Cell Carcinoma Surgical Treatment Disparities in American Indian/Alaska Natives and Hispanic Americans in Arizona.

American Indians/Alaska Natives (AI/AN) and Hispanic Americans (HA) have higher kidney cancer incidence and mortality rates compared to non-Hispanic Whites (NHW). Herein, we describe the disparity in renal cell carcinoma (RCC) surgical treatment for AI/AN and HA and the potential association with mortality in Arizona. A total of 5111 stage I RCC cases diagnosed between 2007 and 2016 from the Arizona Cancer Registry were included. Statistical analyses were performed to test the association of race/ethnicity with surgical treatment pattern and overall mortality, adjusting for patients' demographic, healthcare access, and socioeconomic factors. AI/AN were diagnosed 6 years younger than NHW and were more likely to receive radical rather than partial nephrectomy (OR 1.49 95% CI: 1.07-2.07) compared to NHW. Mexican Americans had increased odds of not undergoing surgical treatment (OR 1.66, 95% CI: 1.08-2.53). Analysis showed that not undergoing surgical treatment and undergoing radical nephrectomy were statistically significantly associated with higher overall mortality (HR 1.82 95% CI: 1.21-2.76 and HR 1.59 95% CI: 1.30-1.95 respectively). Mexican Americans, particularly U.S.-born Mexican Americans, had an increased risk for overall mortality and RCC-specific mortality even after adjusting for neighborhood socioeconomic factors and surgical treatment patterns. Although statistically not significant after adjusting for neighborhood-level socioeconomic factors and surgical treatment patterns, AI/AN had an elevated risk of mortality.

Interrogating Patterns of Cancer Disparities by Expanding the Social Determinants of Health Framework to Include Biological Pathways of Social Experiences.

The objective of this article is to call for integrating biological pathways of social experiences in the concept model of cancer disparities and social determinants of health (SDH) fields. Black, Indigenous, and People of Color (BIPOC) populations experience more negative outcomes across the cancer continuum. Social conditions are instrumental in better understanding the contemporary and historical constructs that create these patterns of disparities. There is an equally important body of evidence that points to the ways that social conditions shape biological pathways. To date, these areas of research are, for the most part, separate. This paper calls for a bridging of these two areas of research to create new directions for the field of cancer disparities. We discuss inflammation, epigenetic changes, co-morbidities, and early onset as examples of the biological consequences of social conditions that BIPOC populations experience throughout their lifespan that may contribute to disproportionate tumorigenesis and tumor progression.

Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes.

BACKGROUND: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health. RESULTS: The discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation ß values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm ß value, the risk of incident CHD increased by 9% in one site and decreased by 6-10% in two sites over 25 years. CONCLUSIONS: Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health.

Racial and Ethnic Disparities in Preoperative Surgical Wait Time and Renal Cell Carcinoma Tumor Characteristics.

Racial/ethnic minority groups have a disproportionate burden of kidney cancer. The objective of this study was to assess if race/ethnicity was associated with a longer surgical wait time (SWT) and upstaging in the pre-COVID-19 pandemic time with a special focus on Hispanic Americans (HAs) and American Indian/Alaska Natives (AIs/ANs). Medical records of renal cell carcinoma (RCC) patients who underwent nephrectomy between 2010 and 2020 were retrospectively reviewed (n = 489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination to date of nephrectomy. Out of a total of 363 patients included, 34.2% were HAs and 8.3% were AIs/ANs. While 49.2% of HA patients experienced a longer SWT (≥90 days), 36.1% of Non-Hispanic White (NHW) patients experienced a longer SWT. Longer SWT had no statistically significant impact on tumor characteristics. Patients with public insurance coverage had increased odds of longer SWT (OR 2.89, 95% CI: 1.53-5.45). Public insurance coverage represented 66.1% HA and 70.0% AIs/ANs compared to 56.7% in NHWs. Compared to NHWs, HAs had higher odds for longer SWT in patients with early-stage RCC (OR, 2.38; 95% CI: 1.25-4.53). HAs (OR 2.24, 95% CI: 1.07-4.66) and AIs/ANs (OR 3.79, 95% CI: 1.32-10.88) had greater odds of upstaging compared to NHWs. While a delay in surgical care for early-stage RCC is safe in a general population, it may negatively impact high-risk populations, such as HAs who have a prolonged SWT or choose active surveillance.

Renal Cell Carcinoma Health Disparities in Stage and Mortality among American Indians/Alaska Natives and Hispanic Americans: Comparison of National Cancer Database and Arizona Cancer Registry Data.

Renal cell carcinoma (RCC) is one of the top 10 cancers in the United States. This study assessed RCC health disparities in American Indians/Alaska Natives (AIs/ANs) and Hispanic Americans (HAs) focusing on advanced-stage and mortality. RCC patients' data were obtained from the National Cancer Database (NCDB) and Arizona Cancer Registry (ACR). Logistic and Cox regression analyses were performed to ascertain the effect of race/ethnicity on stage and mortality, adjusting for neighborhood socioeconomic factors, rural/urban residence pattern, and other factors. In both data sets, AIs/ANs had significantly increased odds of advanced-stage RCC in the unadjusted model, but not in adjusted models. Mexican Americans had higher odds of advanced-stage compared to non-Hispanic Whites in NCDB (OR 1.22, 95% CI: 1.11-1.35) and ACR (OR 2.02, 95% CI: 1.58-2.58), even after adjusting for neighborhood characteristics. AIs/ANs did not show increased mortality risk in NCDB after adjusting for neighborhood characteristics, while the association remained significant in ACR (HR 1.33, 95% CI: 1.03-1.72). The great risk of all-cause and RCC-specific mortality was observed in U.S.-born Mexican Americans in Arizona (HR 3.21, 95% CI: 2.61-3.98 and sub-distribution HR 2.79, 95% CI: 2.05-3.81). RCC disparities in AIs/ANs is partially explained by neighborhood factors, but not in HAs.

Impacting Binational Health through Leadership Development: A Program Evaluation of the Leaders across Borders Program, 2010-2014.

BACKGROUND: Workforce and leadership development is imperative for the advancement of public health along the U.S./Mexico border. The Leaders across borders (LaB) program aims to train the public health and health-care workforce of the border region. The LaB is a 6-month intensive leadership development program, which offers training in various areas of public health. Program curriculum topics include: leadership, border health epidemiology, health diplomacy, border public policies, and conflict resolution. METHODS: This article describes the LaB program evaluation outcomes across four LaB cohort graduates between 2010 and 2014. LaB graduates received an invitation to participate via email in an online questionnaire. Eighty-five percent (n = 34) of evaluation participants indicated an improvement in the level of binationality since participating in the LaB program. Identified themes in the evaluation results included increased binational collaborations and partnerships across multidisciplinary organizations that work towards improving the health status of border communities. Approximately 93% (n = 37) of the LaB samples were interested in participating in future binational projects while 80% (n = 32) indicated interest in the proposal of other binational initiatives. Participants expressed feelings of gratitude from employers who supported their participation and successful completion of LaB. DISCUSSION: Programs such as LaB are important in providing professional development and education to a health-care workforce along the U.S./Mexico border that is dedicated to positively impacting the health outcomes of vulnerable populations residing in this region.

Structural barriers in access to medical marijuana in the USA-a systematic review protocol.

BACKGROUND: There are 43 state medical marijuana programs in the USA, yet limited evidence is available on the demographic characteristics of the patient population accessing these programs. Moreover, insights into the social and structural barriers that inform patients' success in accessing medical marijuana are limited. A current gap in the scientific literature exists regarding generalizable data on the social, cultural, and structural mechanisms that hinder access to medical marijuana among qualifying patients. The goal of this systematic review, therefore, is to identify the aforementioned mechanisms that inform disparities in access to medical marijuana in the USA. METHODS: This scoping review protocol outlines the proposed study design for the systematic review and evaluation of peer-reviewed scientific literature on structural barriers to medical marijuana access. The protocol follows the guidelines set forth by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist. DISCUSSION: The overarching goal of this study is to rigorously evaluate the existing peer-reviewed data on access to medical marijuana in the USA. Income, ethnic background, stigma, and physician preferences have been posited as the primary structural barriers influencing medical marijuana patient population demographics in the USA. Identification of structural barriers to accessing medical marijuana provides a framework for future policies and programs. Evidence-based policies and programs for increasing medical marijuana access help minimize the disparity of access among qualifying patients.

Tuberculosis Treatment Completion in a United States/Mexico Binational Context.

BACKGROUND: Tuberculosis (TB) remains a salient public health issue along the U.S./Mexico border. This study seeks to identify the social and structural factors, which are associated with TB disease burden in the binational geographic region. Identification of barriers of treatment completion provides the necessary framework for developing evidence-based interventions that are culturally relevant and context specific for the U.S./Mexico border region. METHODS: Retrospective study of data extracted from medical charts (n = 439) from Yuma County Health Department (YCHD) (n = 160) and Centro de Salud San Luis Río Colorado (n = 279). Patients currently accessing TB treatment at either facility were excluded from the study. Chi-square, unadjusted odds ratios, and logistic regression were utilized to identify characteristics associated with successful TB treatment in this population. FINDINGS: The study population was predominantly male (n = 327). Females were more likely to complete TB treatment (OR = 3.71). The absence of drug use and/or the absence of an HIV positive diagnosis were found to be predictors of TB treatment completion across both clinical sites. Forty-four percent (43.59%) (n = 85) TB patients treated at CDS San Luis did not complete treatment versus 40.35% (n = 49) of TB patients who did not complete treatment at YCHD. Moving from the area or being deported was the highest category (20.78%) for incomplete TB treatment in the population (n = 64) across both clinical sites.