Nephrectomy Delay of More than 10 Weeks from Diagnosis Is Associated with Decreased Overall Survival in pT3 RCC

In this study, we aimed to evaluate the impact of surgical wait time (SWT) on outcomes of patients with renal cell carcinoma (RCC), and to investigate risk factors associated with prolonged SWT. Using the National Cancer Database, we retrospectively reviewed the records of patients with pT3 RCC treated with radical or partial nephrectomy between 2004 and 2014. The cohort was divided based on SWT. The primary outcome was 5-year overall survival (OS). Logistic regression analysis was used to investigate the risk factors associated with delayed surgery. Cox proportional hazards models were fitted to assess relations between SWT and 5-year OS after adjusting for confounding factors. A total of 22,653 patients were included in the analysis. Patients with SWT > 10 weeks had higher occurrence of upstaging. Using logistic regression, we found that female patients, African-American or Spanish origin patients, treatment in academic or integrated network cancer center, lack of insurance, median household income of <$38,000, and the Charlson–Deyo score of ≥1 were more likely to have prolonged SWT. SWT > 10 weeks was associated with decreased 5-year OS (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.15–1.33). This risk was not markedly attenuated after adjusting for confounding variables, including age, gender, race, insurance status, Charlson–Deyo score, tumor size, and surgical margin status (adjusted HR, 1.13; 95% CI, 1.04–1.24). In conclusion, the vast majority of patients underwent surgery within 10 weeks. There is a statistically significant trend of increasing SWT over the study period. SWT > 10 weeks is associated with decreased 5-year OS

Selenium supplementation and insulin resistance in a randomized, clinical trial

Objective: While controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic beta-cell function and insulin sensitivity. Research design and methods: In a subset of 400 individuals participating in a randomized, placebocontrolled trial of Se at 200 mu g/day for colorectal adenomatous polyps, fasting plasma glucose and insulin were measured before randomization and within 6 months of completing intervention. Change in the homeostasis model assessment-beta cell function (HOMA2-%beta) and insulin sensitivity (HOMA2-%S) were compared between arms. A subgroup of 175 (79 Se and 96 placebo) participants underwent a modified oral glucose tolerance test (mOGTT) at the end of intervention and change in glucose values was assessed. Results: No statistically significant differences were observed for changes in HOMA2-%beta or HOMA2-%S between those who received Se compared with placebo. After a mean of 2.9 years on study, mean HOMA2-%beta values were 3.1 +/- 24.0 and 3.1 +/- 29.8 for the Se and placebo groups, respectively (p=0.99). For HOMA2-%S, the values were -0.5 +/- 223.2 and 80.9 +/- 1530.9 for the Se and placebo groups, respectively (p=1.00). Stratification by sex or age did not reveal any statistically significant effects on insulin sensitivity by treatment group. For mOGTT, mean baseline fasting blood glucose concentrations were significantly higher among participants in the placebo group compared with the Se group (96.6 +/- 14.6 and 92.3 +/- 12.0, respectively; p=0.04), a trend which remained through the 20 min assessment. Conclusions: These findings do not support a significant adverse effect of daily Se supplementation with 200 mu g/day of selenized yeast on beta-cell function or insulin sensitivity as an explanation for previously reported associations between Se and T2D. Further clarification of longer term effects of Se is needed.National Cancer Institute Cancer Center Support Grant [P30 CA023074]; NIH/NCI [R01CA151708, P01 CA041108]; NIH [R01DK047396]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Digital image analysis using video microscopy of human-derived prostate cancer vs normal prostate organoids to assess migratory behavior on extracellular matrix proteins

The advent of perpetuating living organoids derived from patient tissue is a promising avenue for cancer research but is limited by difficulties with precise characterization. In this brief communication, we demonstrate via time-lapse imaging distinct phenotypes of prostate organoids derived from patient material– without confirmation of cellular identity. We show that organoids derived from histologically normal tissue more readily spread on a physiologic extracellular matrix (ECM) than on pathologic ECM (p<0.0001), while tumor-derived organoids spread equally on either substrate (p=0.2406). This study is an important proof-of-concept to defer precise characterization of organoids and still glean information into disease pathology

Effects of Female Gene Flow and Effective Population Size on Old and New World Mitochondrial DNA Patterns

The goal of this dissertation project is to examine the effects of female gene flow and female effective population size on mtDNA variation. I examined 1) whether the Aymara and Bantu expanded mainly through spatial expansion by incorporating female migrants from other ethnic groups or through demographic expansion due to increased female fertility rates, 2) whether female gene flow or effective population size had the greater effect on mtDNA within-population genetic diversity, and 3) the extent to which kinship structure affected the importance of each factor. The results of the analyses suggest rapid demographic expansion best explains Aymara population expansion. Female gene flow was also an important factor influencing mtDNA variation in Central Andeans as well as western South America, but female gene flow had a much greater impact on mtDNA variation among east African Bantu populations. The east African Bantu populations interacted extensively with neighboring non-Bantu populations. As a result, the east African Bantus became genetically more diverse and similar to some non-Bantu east Africans. Closer examination of the impact of female gene flow and effective population size reveals that female gene flow affects within-population genetic diversity measurements and genetic models that do not account for population subdivision and gene flow are poor fits to the observed mtDNA data. In addition, kinship structure is an important cultural practice that affects the patterns and intensity of female gene flow and is a good predictor of within-population genetic diversity and population subdivision. In conclusion, this dissertation project shows that female effective population is an important factor, but female gene flow had a great impact on mtDNA variation among Latin Americans and Bantus affecting their within-population genetic diversity and patterns of population subdivision

Leveraging genetic ancestry to study health disparities

Research to understand human genomic variation and its implications in health has great potential to contribute in the reduction of health disparities. Biological anthropology can play important roles in genomics and health disparities research using a biocultural approach. This paper argues that racial/ethnic categories should not be used as a surrogate for sociocultural factors or global genomic clusters in biomedical research or clinical settings, because of the high genetic heterogeneity that exists within traditional racial/ethnic groups. Genetic ancestry is used to show variation in ancestral genomic contributions to recently admixed populations in the United States, such as African Americans and Hispanic/Latino Americans. Genetic ancestry estimates are also used to examine the relationship between ancestry-related biological and sociocultural factors affecting health disparities. To localize areas of genomes that contribute to health disparities, admixture mapping and genome-wide association studies (GWAS) are often used. Recent GWAS have identified many genetic variants that are highly differentiated among human populations that are associated with disease risk. Some of these are population-specific variants. Many of these variants may impact disease risk and help explain a portion of the difference in disease burden among racial/ethnic groups. Genetic ancestry is also of particular interest in precision medicine and disparities in drug efficacy and outcomes. By using genetic ancestry, we can learn about potential biological differences that may contribute to the heterogeneity observed across self-reported racial groups.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Association between Serum 25-Hydroxy-Vitamin D and Aggressive Prostate Cancer in African American Men

African American men have higher incidence rates of aggressive prostate cancer, where high levels of calcium and serum vitamin D deficient levels play a role in the racial differences in incidence. In this study, we examined associations of serum vitamin D with aggressive prostate cancer to improve our understanding of higher susceptibility of aggressive disease in this racial cohort. From Howard University Hospital, 155 African American men with clinically-identified prostate cancer were identified; 46 aggressive cases, and 58 non-aggressive cases. Serum vitamin D was assessed from fasting blood samples, and total calcium intake was assessed using the Block Food Frequency Questionnaire. Vitamin D receptor polymorphisms from three different loci were genotyped; rs731236, rs1544410, and rs11568820. Multivariate logistic regression models were used to determine odds ratios (OR) and 95% confidence intervals (CI) comparing aggressive to non-aggressive prostate cancer. Vitamin D deficiency (<20 ng/mL) significantly increased risk of aggressive disease (OR: 3.1, 95% CI: 1.03–9.57, p-value = 0.04). Stratification by total calcium showed high calcium levels (≥800 mg/day) modified this association (OR: 7.3, 95% CI: 2.15–47.68, p-interaction = 0.03). Genetic variant rs11568820 appeared to increase the magnitude of association between deficient serum vitamin D and aggressive prostate cancer (OR: 3.64, 95% CI: 1.12–11.75, p-value = 0.05). These findings suggest that high incidence of aggressive prostate cancer risk in African American men may be due in-part to deficient levels of serum vitamin D. Other factors, including genetics, should be considered for future studies

Clinical and Molecular Characteristics and Burden of Kidney Cancer Among Hispanics and Native Americans: Steps Toward Precision Medicine

Cancer disparities in Native Americans (NAs) and Hispanic Americans (HAs) vary significantly in terms of cancer incidence and mortality rates across geographic regions. This review reports that kidney and renal pelvis cancers are unevenly affecting HAs and NAs compared to European Americans of non-Hispanic origin, and that currently there is significant need for improved data and reporting to be able to advance toward genomic-based precision medicine for the assessment of such cancers in these medically underserved populations. More specifically, in states along the US-Mexico border, HAs and NAs have higher kidney cancer incidence rates as well as a higher prevalence of kidney cancer risk factors, including obesity and chronic kidney disease. They are also more likely to receive suboptimal care compared to European Americans. Furthermore, they are underrepresented in epidemiologic, clinical, and molecular genomic studies of kidney cancer. Therefore, we maintain that progress in precision medicine for kidney cancer care requires an understanding of various factors among HAs and NAs, including the real kidney cancer burden, variations in clinical care, issues related to access to care, and specific clinical and molecular characteristics.(C) 2018 Elsevier Inc. All rights reserved.American Cancer Society [IRG-16-124-37-IRG]12 month embargo; published online: 12 February 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Patterns of Cancer Related Health Disparities in Arizona

Cancer incidence rates vary regionally among American Indians (AIs) and Latinos.  The goal of this was to identify areas of research necessary to reduce cancer health disparities in AIs and Latinos, the two major racial/ethnic minority groups in Arizona.  In an effort to better understand cancer health disparities, cancer incidence rates in AIs and Latinos in Arizona were compared to non-Hispanic Whites (NHWs).  Age-adjusted incidence rates (per 100,000) were obtained from the Arizona Cancer Registry and the North American Association of Central Cancer Registries.  Spearman’s rank test was used to examine correlation between county-level cancer incidence rates and socio-demographic factors.  AIs and Latinos had lower incidence rates of screening for detectable cancers than NHWs.  Among older men (age ≥65), however, AIs and Latinos had similar prostate cancer incidence rates to NHWs.  Some of less common cancers, such as kidney, stomach, liver, and gallbladder, were more frequently diagnosed in AIs and Latinos than NHWs.  AIs and Latinos were more likely to be diagnosed with advanced cancer stage, except for cervical cancer.  Correlations between prostate and breast cancer incidence rates and percent urban residents as well as population size were significantly positive.  Poverty levels were inversely correlated with colorectal and lung cancer incidence rates.  Our review of cancer incidence rates suggests that socio-demographic factors, such as population size (rural/urban) and poverty levels, have influenced cancer detection and incidence rates in Arizona.&nbsp