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Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of

PDF file, 117K, -Log10 P-value plot of genotyped SNPs in IL-16 (±250kb) region in Washington, D.C. AA discovery samples.

PDF file, 114K, LD plots of the 11 SNPs in 1000 genome European population.

PDF file, 98K, Fine-mapping of IL16 gene and prostate cancer risk in African Americans.

Background: Prostate cancer is the most common type of cancer among men in the United States, and its incidence and mortality rates are disproportionate among ethnic groups. Although genome-wide association studies of European descents have identified candidate loci associated with prostate cancer risk, including a variant in IL16, replication studies in African Americans (AA) have been inconsistent. Here we explore single-nucleotide polymorphism (SNP) variation in IL16 in AAs and test for association with prostate cancer.Methods: Association tests were conducted for 2,257 genotyped and imputed SNPs spanning IL16 in 605 AA prostate cancer cases and controls from Washington, D.C. Eleven of them were also genotyped in a replication population of 1,093 AAs from Chicago. We tested for allelic association adjusting for age, global and local West African ancestry.Results: Analyses of genotyped and imputed SNPs revealed that a cluster of IL16 SNPs were significantly associated with prostate cancer risk. The strongest association was found at rs7175701 (P = 9.8 × 10−8). In the Chicago population, another SNP (rs11556218) was associated with prostate cancer risk (P = 0.01). In the pooled analysis, we identified three independent loci within IL16 that were associated with prostate cancer risk. SNP expression quantitative trait loci analyses revealed that rs7175701 is predicted to influence the expression of IL16 and other cancer-related genes.Conclusion: Our study provides evidence that IL16 polymorphisms play a role in prostate cancer susceptibility among AAs.Impact: Our findings are significant given that there has been limited focus on the role of IL16 genetic polymorphisms on prostate cancer risk in AAs. Cancer Epidemiol Biomarkers Prev; 21(11); 2059–68. ©2012 AACR.

PDF file, 204K, LD plot of the top 30 genotyped and imputed SNPs generated with 1000 Genomes YRI genotype data.

PDF file, 122K, -log10 P-value plot of association tests after imputation masking 24 genotyped SNPs. In this analysis, rs7175701 was masked and imputed yet remained the most significant SNP.

PDF file, 93K, Assessment of imputation accuracy and results of imputation.

PDF file, 125K, -log10 P-value plot of association tests using genotyped and imputed SNPs from MACH and HapMap data analysis showing that the same three SNPs have the strongest association.

PDF file, 93K, Distribution of percent global West African Ancestry estimates in the discovery and replication cases (mean global WAA in discovery cases = 81.2%, mean global WAA in replication cases = 79.1 %; T-test P=0.342).

Background There are no series evaluating penile squamous cell carcinoma (pSCC) based on human papillomavirus (HPV) infection. Herein, we present national registry data on clinical and survival outcomes for pSCC based on HPV status. Methods We performed a retrospective review of 1224 pSCC patients with known HPV staining from the National Cancer Database. Patients with cM1 disease, those who did not receive treatment, or had missing follow‐up data were excluded. Logistic regression identified factors associated with locally aggressive disease. Univariable, multivariable, and inverse probability of treatment weighting (IPTW)‐Cox proportional hazard modeling were used to assess hazard ratios (HR) associated with overall survival (OS). Results After exclusion criteria, we identified 825 cases of which 321 (38.9%) were HPV positive. The HPV‐positivity rate did not significantly change by year. HPV‐positive patients were younger, had lower Charlson‐Deyo performance score, and resided in areas with both lower median household income and lower school education completion. HPV‐positive tumors presented with lower American Joint Committee on Cancer clinical T‐stage (cT), poorer differentiation, lower rates of lymphovascular invasion (LVI), but more node‐positive disease (cN+). For those who underwent lymph node surgery, there were no differences in final pathologic stage, upstaging, or presence of extranodal extension. Only tumor differentiation, LVI, and performance score were independent predictors for locally aggressive disease. HPV status was not a predictor of OS (IPTW‐HR:0.89, p = 0.13). Conclusions In the largest series evaluating pSCC based on HPV status, HPV‐positive tumors were associated with lower cT stages, less LVI, but more cN + disease. More studies on prognostic factors are needed, and time may still be immature to use HPV information for risk stratification., Infection with human papillomavirus (HPV) is endemic and a causative agent for several malignancies in both male and female populations. In this study, we queried a large, cancer registry to look for clinical and survival differences between HPV‐positive versus negative penile tumors. Our results noted a lack of prognostic impact for HPV‐derived tumors, although more studies will be required to validate results.

The American Cancer Society (ACS) estimated more than 1.8 million new cancer cases in the US in 2020, and about 1.7 million cancer survivors. This chapter presents information on childhood, adolescent and young adult (AYA), and adult cancers in American Indians, Alaska Natives, Native Hawaiians and Pacific Islanders. Clinical trials are the best source for state-of-the art care, but Indigenous Peoples, especially Indigenous children and adolescents, are under-represented in cancer clinical trials. Community-engaged examples highlight a program in South Dakota to increase American Indian enrollment in clinical trials, a study to increase cancer screening among Hopi men, a website for Native cancer survivors, and a project to improve colorectal cancer screening among Alaska Natives.

To analyze utilization and outcomes of cytoreductive surgery (CRS) after systemic chemotherapy in select patients with metastatic upper tract urothelial carcinoma (UTUC).We identified 1,73 patients with cM1 UTUC from the National Cancer Database who were treated with first-line multiagent chemotherapy from 2004 to 2015. Patients considered surgical candidates based on Charlon-Deyo performance score were stratified into nonsurgical versus surgical arms based on receipt of CRS after systemic therapy. Those receiving radiation, immunotherapy, or other types of treatment were excluded. Cox proportional hazard models were used to analyze prognostic factors for overall survival (OS). Propensity-score matching and inverse probability of treatment weighting-adjusted regression models were used to compare OS.A total of 1182 patients were included of which 349 (29.5%) were treated with definitive surgery. Median follow-up was 64 months (95% confidence interval:49.8-79.4) for chemotherapy+surgery versus 61.2 (52.2-78.7) for the chemotherapy-alone arms (P = .09). Patients treated with surgery were younger and more commonly treated at academic facilities. Patients who received CRS had improved median-OS versus those treated with chemotherapy alone (13.7 vs 10.8 months, log-rank P-value.001). Predictors of OS were performance score, treatment at academic facility, and performance of CRS. Furthermore, in propensity-score and inverse probability of treatment weighting-adjusted Cox regression analyses, CRS was associated with significant OS benefit (hazard ratios = 0.61, 95% confidence interval:0.49-0.77, and 0.63;0.55-0.72; respectively).We provide a contemporary report on the survival benefit of CRS after treatment with systemic therapy for M1 UTUC patients. Longitudinal studies are needed to evaluate the role of surgery, when feasible, within multidisciplinary approaches for this relatively, rare disease.

Background: Although there is increased awareness leading to early detection and prevention, Hispanic American (HA) men with prostate cancer (PC) continue to have greater mortality rates compared to their Non-Hispanic White (NHW) counterparts. Moreover, HA men with PC are more likely to have more advanced disease compared to NHW men. Here, we characterized the molecular and immune differences in HA and NHW tumors and their association with PC ethnic disparity. Methods: 88 PC samples (HA=34, NHW=54) obtained from treatment-naive metastatic hormone-sensitive PC (mHSPC) were analyzed by next-generation sequencing (592, NextSeq; WES, NovaSeq), Whole Transcriptome Sequencing (WTS; NovaSeq) (Caris Life Sciences, Phoenix, AZ). AR signature and NEPC score were calculated based on the expression level of previously defined genes (Hieronymus et al. 2006, Beltran et al. 2016). Medical record was reviewed in a deidentified fashion for clinal features. Statistical significance was determined using chi-square and Mann-Whitney U (p Results: HA patients with PC had higher level of PSA (111.5 vs 52.6 ng/ml, p=0.12) and stage (T4: 41% vs 14% p=0.01, M1c: 41% vs 16% p=0.04) but no significant difference in frequency of Gleason score > 4 (79% vs 73%, p=0.61) or stage N1 (69% vs 61%, p=0.85) compared to NHW. HA PC had a significantly higher frequency of TMPRSS2-fusion (46.4% vs 20.0%, p=0.04) compared to NHW PC. By Gene Set Enrichment Analysis, HA PC had enrichment of KRAS signaling (NES: 1.44, FDR=0.02), Hedgehog signaling (NES: 1.45, FDR=0.04), NOTCH signaling (NES: 1.41, FDR=0.07), Hypoxia (NES: 1.38, FDR=0.10) and IL2-STAT5 signaling (NES: 1.35, FDR=0.10) pathways compared to NHW tumors. There was no difference in median Androgen Receptor signature (p=0.78) or Neuroendocrine Prostate Cancer (NEPC) score (p=0.79). Also, no significant difference in AR positivity by IHC (100% vs 95.7%) between HA and NHW PC tumors (p=0.51). HA PC had significantly higher expression of stem cell markers ALDH1A1 (2.1-fold), ALDH1A2 (3-fold), and PROM1 (1.6-fold) and immunoinhibitory genes PDCD1LG2 (1.68-fold) and FOXP3 (1.45-fold) compared to NHW tumors (all p Conclusion: Our data suggest that HA mHSPC is associated with higher levels of PSA, stage, TMPRSS2-fusions, stemness marker expression, immunoinhibitory gene expression, and increased M1 Macrophage and NK cell infiltration. Together, these findings suggest a crucial role of differential molecular and tumor immune microenvironment in PC ethnic disparity. A better understanding of these differences with additional research may help in designing the approaches for reducing the ethnic disparities gaps in PC patients. Citation Format: Alejandro Recio-Boiles, Sachin Kumar Deshmukh, Juan Chipollini, Ken Batai, Sharon Wu, Joanne Xiu, Alex Farrell, Milan Radovich, Elisabeth Heath, Rana McKay, Chadi Nabhan. Molecular characterization of prostate cancer between Hispanic American and Non-Hispanic Whites: Implications for cancer ethnic health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1895.

BACKGROUND: Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation. OBJECTIVES: A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. METHODS: A total of 428 participants aged 40–80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200 µg of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations. RESULTS: No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P = 4.41 × 10(−7)), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P = 0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P = 8.67 × 10(−8)). CONCLUSIONS: This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.

Cancer screening rates among American Indian men remain low, without programs specifically designed for men. This paper describes the Community-Based Participatory Research processes and assessment of cancer screening behavior and the appropriateness of the mHealth approach for Hopi men’s promotion of cancer screenings. This Community-Based Participatory Research included a partnership with H.O.P.I. (Hopi Office of Prevention and Intervention) Cancer Support Services and the Hopi Community Advisory Committee. Cellular phone usage was assessed among male participants in a wellness program utilizing text messaging. Community surveys were conducted with Hopi men (50 years of age or older). The survey revealed colorectal cancer screening rate increased from 51% in 2012 to 71% in 2018, while prostate cancer screening rate had not changed (35% in 2012 and 37% in 2018). Past cancer screening was associated with having additional cancer screening. A cellular phone was commonly used by Hopi men, but not for healthcare or wellness. Cellular phone ownership increased odds of prostate cancer screening in the unadjusted model (OR 9.00, 95% CI: 1.11–73.07), but not in the adjusted model. Cellular phones may be applied for health promotion among Hopi men, but use of cellular phones to improve cancer screening participation needs further investigation.

BackgroundInflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling.MethodsWe conducted a phase 2 open-label study of intravenous tocilizumab (8 mg·kg−1) over 6 months in patients with group 1 PAH. Co-primary end-points were safety, defined by incidence and severity of adverse events, and change in pulmonary vascular resistance. Separately, a mendelian randomisation study was undertaken on 11 744 individuals with European ancestry including 2085 patients with idiopathic/heritable disease for the IL-6 receptor (IL6R) variant (rs7529229), known to associate with circulating IL-6R levels.ResultsWe recruited 29 patients (male/female 10/19; mean±sd age 54.9±11.4 years). Of these, 19 had heritable/idiopathic PAH and 10 had connective tissue disease-associated PAH. Six were withdrawn prior to drug administration; 23 patients received at least one dose of tocilizumab. Tocilizumab was discontinued in four patients owing to serious adverse events. There were no deaths. Despite evidence of target engagement in plasma IL-6 and C-reactive protein levels, both intention-to-treat and modified intention-to-treat analyses demonstrated no change in pulmonary vascular resistance. Inflammatory markers did not predict treatment response. Mendelian randomisation did not support an effect of the lead IL6R variant on risk of PAH (OR 0.99, p=0.88).ConclusionAdverse events were consistent with the known safety profile of tocilizumab. Tocilizumab did not show any consistent treatment effect.

Cancer screening rates remain low among American Indian men, and cancer screening behaviors and barriers to cancer screening among American Indian men are not well understood. This study evaluated cancer screening behaviors in 102 Hopi men who were 50 years of age or older from the Hopi Survey of Cancer and Chronic Disease. Reported cancer screening frequencies were 15.7%, 45.1%, and 35.3% for Fecal Occult Blood Test (FOBT), colonoscopy, and Prostate Specific Antigen (PSA) test, respectively. Among men who reported having had a FOBT, 81.2% had the test more than one year ago. Among men who reported a colonoscopy, 60.8% had colonoscopy within the past three years. Similarly, among men who reported having had PSA, 72.3% had PSA within the past three years. “No one told me” was the most common answer for not undergoing FOBT (33.7%), colonoscopy (48.2%), and PSA (39.4%). Men who reported having had a PSA or digital rectal exam were three times as likely to also report having a FOBT or colonoscopy (odds ratio [OR] 3.19, 95% confidence interval [CI]: 1.21–8.46). Younger age (

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., Special Issue: Race reconciled II: Interpreting and communicating biological variation and race in 2021

Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Methods: Patients with Group 1 PAH were included from two national registries with genome-wide data and two local cohorts, and further incorporated in a global meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for transplant-free, all-cause mortality in Hispanic patients with non-Hispanic white (NHW) patients as the reference group. Odds ratios (ORs) for inpatient-specific mortality in patients with PAH were also calculated for race/ethnic groups from an additional National Inpatient Sample dataset not included in the meta-analysis.Measurements and Main Results: After covariate adjustment, self-reported Hispanic patients (n = 290) exhibited significantly reduced mortality versus NHW patients (n = 1,970) after global meta-analysis (HR, 0.60 [95% CI, 0.41-0.87]; P = 0.008). Although not significant, increasing Native American genetic ancestry appeared to account for part of the observed mortality benefit (HR, 0.48 [95% CI, 0.23-1.01]; P = 0.053) in the two national registries. Finally, in the National Inpatient Sample, an inpatient mortality benefit was also observed for Hispanic patients (n = 1,524) versus NHW patients (n = 8,829; OR, 0.65 [95% CI, 0.50-0.84]; P = 0.001). An inpatient mortality benefit was observed for Native American patients (n = 185; OR, 0.38 [95% CI, 0.15-0.93]; P = 0.034).Conclusions: This study demonstrates a reproducible survival benefit for Hispanic patients with Group 1 PAH in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.

Racial/ethnic minority groups in the United States have high renal cell carcinoma (RCC) mortality rates. This study assessed surgical treatment disparities across racial/ethnic groups and impacts of neighborhood socioeconomic characteristics on surgical treatments and overall mortality. Stage I RCC patients diagnosed between 2004 and 2016 from National Cancer Database were included (n = 238,141). We assessed differences in associations between race/ethnicity and treatment patterns using logistic regression and between race/ethnicity and overall mortality using Cox regression with and without neighborhood characteristics in the regression models. When compared to non-Hispanic Whites (NHWs), American Indians/Alaska Natives and non-Hispanic Blacks (NHBs) were more likely not to receive surgical care and all racial/ethnic minority groups had significantly increased odds of undergoing radical rather than partial nephrectomy, even after adjusting for neighborhood characteristics. Including surgical treatment and neighborhood factors in the models slightly attenuated the association, but NHBs had a significantly increased risk of overall mortality. NHBs who underwent radical nephrectomy had an increased risk of mortality (HR 1.15, 95% CI: 1.08–1.23), but not for NHBs who underwent partial nephrectomy (HR 0.92, 95% CI: 0.84–1.02). Neighborhood factors were associated with surgical treatment patterns and overall mortality in both NHBs and NHWs. Neighborhood socioeconomic factors may only partly explain RCC disparities.

30 Background: Genomic testing through the employment of somatic and germline testing has become increasingly relevant in determining the prognosis and targeted therapies for advanced prostate cancer patients. Prostate cancer health disparities resulting in worse presentations and clinical outcomes have been observed in HA compared to NHW. Understanding the prevalence of different genomic alterations is paramount to bridge the gap between the two ethnic groups. Methods: This is a retrospective analysis of 190 metastatic prostate adenocarcinoma patients with 24.2% HA who presented to the University of Arizona Cancer Center from 2015 to 2022. Patients in both groups may have undergone more than one type of testing. Homologous recombination repair (HRR) included ATM, BRCA1/2, BARD1, BRIP1, CDK12, CHEK1/2, FANCA/L, HDAC2, PALB2, RAD-51B/1C/51D, or 54L. Tissue-agnostic therapy approvals are dMMR, MSI-H, TMB-High, BRAF V600E, and NTRK/RET fusion. The proportion of HA and NHW was determined, and the statistical significance of the differences was reported using Chi2 or Fisher’s Exact test. Results: 43.6%, 34.7%, and 38.9% of patients had somatic tissue, liquid, and germline testing, respectively analyzed for pathogenic variants. TMB-High >10 (30% vs 3.6%, p=0.02), PD-L1 CPS>5 (9.4% vs 0%, p=0.03) and TMPRSS2-ERG fusion (37.5 vs 7.8%, p=0.0009) had higher proportion in HA compared to NHW. No test showed a difference in BRCA 1/2 or another HRR deficiency actionable mutation between the two ethnicities. There were no other statistically significant differences in common mutations or variants of unknown significance among groups. Conclusions: Liquid and tissue biopsies indicated a difference in proportions for tissue-agnostic and immune-oncology therapeutic indications, being more prevalent in HA. TMPRSS2-ERG fusions have differences in PC development and progression by race and now potentially by ethnicity, as shown by our study. Our review revealed increased germline and somatic testing over time according to targeted therapies approval and guideline recommendations, although, there remains a critical need for advancing genomic sequencing efforts for underrepresented HA. The Hispanic Americans Prostate Cancer Comprehensive Genomic Profiling Study's (THAPCA-GPS) future investigations aim to delineate the pathogenetic differences between HA and NHW and may reduce healthcare disparities and improve clinical outcomes in HA patients. [Table: see text]

31 Background: Multiple retrospective studies conducted have demonstrated disparities in access to care and treatment rates for prostate cancer between HA and NHW. We sought to understand the differences in prostate cancer presenting characteristics, prognosis, and outcomes between the two ethnic groups who presented to the University of Arizona Cancer Center (UACC), which serves a large Hispanic community. Methods: A retrospective analysis of mHSPC adenocarcinoma patients who presented to UACC from 2016 to 2022 was conducted. Patients must have had genetic testing to be included. Patients with no metastasis and incomplete data were excluded. Continuous data were analyzed using t-tests or Wilcoxon Rank sum tests depending on whether they were normally distributed. Categorical variables were analyzed using X2 Tests or Fisher's exact tests. Time to Event data was analyzed using Kaplan-Meier Methods. Results: 83 patients were included with 38.5% HA. No difference was observed between the ethnic groups by median age at presentation (66 years), race (90% white), obesity (40% BMI>30), personal cancer history (10%), or family history of cancer (48%). HA were more likely to have a smoking (69%) and alcohol (63%) history compared to NHW (54% and 39%, respectively; p= 0.04). On presentation, 56% of HA were ECOG 0 compared to 22% of NHW (p=0.001). At the time of diagnosis, HA had median PSA levels of 111.5 ng/ml compared to 52.6 ng/ml in NHW (p=0.12). Gleason Grade Group ≥4 in 73% HA vs 79% in NHW (p=0.61). 41% of HA presented with T4 disease compared to 14% of NHW (p=0.01). 69% of HA presented with N1 disease vs 61% of NHW (p=0.85). 41% of HA presented with visceral metastasis, M1c, compared to 16% of NHW (p=0.04). The median time to first-line (1L) treatment was 1 month in HA compared to 3 months for NHW (p

Background: Hispanic Americans (HAs) and American Indians (AIs) in Arizona experience marked disparities in renal cell carcinoma (RCC) with a younger age at diagnosis, higher stage, and higher mortality rates compared to non-Hispanic Whites (NHWs). The underlying factors causing the disparities are still under investigation. This study explored relationships between neighborhood characteristics, race/ethnicity, and obesity in RCC patients. Methods: Medical records of patients who underwent RCC surgical treatment between 2010 and 2021 at Banner University Medical Center Tucson/University of Arizona were reviewed. Social Deprivation Index (SDI) score was calculated using American Community Survey data and linked to the zip code of patient’s residence. Logistic regression analysis was performed to assess associations of SDI, race/ethnicity, and BMI with RCC characteristics and perioperative outcomes. Results: A total of 379 patients (49.9% NHWs, 34.6% HAs, and 7.4% AIs) with SDI data were included in this study. They lived in 116 zip code areas (86 in NHWs, 49 in HAs, and 13 in AIs). 18 patients (4.7%) lived in the most common zip code area. 51.7% of zip codes had only one patient living in the area. HAs and AIs were more likely to have an earlier age of diagnosis and higher BMI and live in high SDI neighborhoods compared to NHWs. SDI were positively associated with BMI in the total dataset and HAs, but not in NHWs. HA ethnicity and high BMI were significantly associated with earlier age of diagnosis. HAs had increased odds of having clear cell RCC, but the association was not significant after adjusting for SDI. HAs had an increased odds of clear cell RCC only in patients living in high SDI neighborhoods (OR 3.33, 95% CI 1.00-11.07). In patients living in low SDI neighborhoods, HAs had increased odds of advanced stage (OR 2.52, 95% CI 1.17-5.45), but not in patients living high SDI neighborhoods (P-interaction=0.02). BMI≥35 was associated with advanced stage in NHWs (OR 3.08, 95% CI 1.14-8.35), but not in HAs (P-interaction=0.07). SDI was not associated with advanced stage. SDI was associated with high grade in NHWs (OR 3.08, 95% CI 1.14-8.35), but not in HAs (P-interaction=0.06). Next, we investigated impacts of obesity on perioperative outcomes adjusting for SDI. BMI≥35 was associated with a longer ischemia time (OR 3.41, 95% CI 1.06-11.2), and this association was stronger in patients living in low SDI than high SDI neighborhoods and in HAs than NHWs. HAs with BMI 30-35 had increased odds (OR 7.83, 954% CI 1.18-51.81) of a greater estimated blood loss during the surgery. Patients with BMI 25-30 had significantly increased odds (OR 6.95 95% CI 1.18-41.00) of longer hospital stay after surgery. A stronger association was observed in NHWs, and the association was not significant in HAs. Conclusion: This study revealed that SDI is an underlying factor of obesity in RCC patients. The relationships between SDI, race/ethnicity, and obesity are complex, and obesity is impacting racial/ethnic groups differently. Citation Format: Ken Batai, Waheed Asif, Patrick Wightman, Alejandro Cruz, Celina I. Valencia, Francine C. Gachupin, Chiu-Hsieh Hsu, Juan Chipollini, Benjamin R. Lee. Intersectionality of neighborhood socioeconomic deprivation, race/ethnicity, and obesity in renal cell carcinoma disparities in Hispanics and American Indians in Arizona [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C085.

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.

Prostate cancer (PCa) is the second most frequently diagnosed malignancy and the second leading cause of death in men worldwide, after adjusting for age. According to the International Agency for Research on Cancer, continents such as North America and Europe report higher incidence of PCa; however, mortality rates are highest among men of African ancestry in the western, southern, and central regions of Africa and the Caribbean. The American Cancer Society reports, African Americans (AAs), in the United States, have a 1.7 increased incidence and 2.4 times higher mortality rate, compared to European American’s (EAs). Hence, early population history in west Africa and the subsequent African Diaspora may play an important role in understanding the global disproportionate burden of PCa shared among Africans and other men of African descent. Nonetheless, disparities involved in diagnosis, treatment, and survival of PCa patients has also been correlated to socioeconomic status, education and access to healthcare. Although recent studies suggest equal PCa treatments yield equal outcomes among patients, data illuminates an unsettling reality of disparities in treatment and care in both, developed and developing countries, especially for men of African descent. Yet, even after adjusting for the effects of the aforementioned factors; racial disparities in mortality rates remain significant. This suggests that molecular and genomic factors may account for much of PCa disparities.

INTRODUCTION AND OBJECTIVE: Natural and humancaused disasters, such as the COVID-19 pandemic, often have bigger negative effects on health status and healthcare access of racial/ethnic minority patients. The purpose of this study was two-fold, to assess if 1) a longer surgical wait time (SWT, ≥ 90 days) affects renal cell carcinoma (RCC) tumor characteristics at nephrectomy and 2) race/ethnicity was associated with a longer SWT and upstaging in the pre-COVID-19 pandemic time with focus on Hispanic Americans (HAs) and Native Americans (NAs) who have heavier burden of RCC in Arizona. METHODS: Medical records of patients diagnosed with RCC who underwent nephrectomy between 2010 and 2020 (through March, before the COIVD-19 pandemic worsened) at Banner-University Medical Center Tucson were reviewed (n=489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination (e.g., CT and MRI) to date of nephrectomy. Logistic regression analysis was performed to assess if race/ethnicity was associated with longer SWT or upstaging. RESULTS: A total of 393 patients were included, 34.2% and 8.3% of patients were HAs and NAs respectively. While 49.2% of HA patients had a longer SWT, only 36.1% of non-Hispanic White (NHW) patients had a longer SWT. Longer SWT did not have a significant impact on tumor characteristics. Tumor size increased (≥ 2cm) in 9.9% of patients with a longer SWT, while 8.9% of patients with a shorter SWT had increased tumor size. Pathologic upstaging was seen in 26.4% and 25.7% of patients with longer and shorter SWT, respectively. Patients with public insurance coverage had increased odds of longer SWT (OR, 2.89;95% CI: 1.53-5.45). Public insurance coverage was higher among HAs and NAs, representing 66.1% and 70.0% of coverage compared to 56.7% in NHWs. Compared to NHWs, HAs had significantly increased odds of a longer SWT in patients with early-stage RCC (TNM Stage I or II) (OR 2.38, 95% CI: 1.25-4.53). HAs and NAs had increased odds of upstaging (OR 2.24, 95% CI: 1.07-4.66 for HAs and OR 3.79, 95% CI: 1.32-10.88 for NAs). Among patients with

INTRODUCTION AND OBJECTIVE:Tyrosine kinase inhibitors (TKI) have the theoretical advantage of downsizing renal cell carcinoma (RCC) to facilitate nephron-sparing surgery while preserving renal func...

Background Benign prostatic obstruction (BPO) due to benign prostatic hyperplasia (BPH) is a leading cause of morbidity in men over the age of 40. This study examined whether there was an association between body mass index (BMI) and pre-operative prostate volume and whether expression of two genes, alpha-2-macroglobulin (A2M) and transforming growth factor beta 3 (TGFB3), was correlated with BMI, pre-operative prostate volume, and age at surgery. Methods Medical records of patients who underwent holmium enucleation of the prostate surgery for treatment of BPO were retrospectively reviewed. Surgical specimens were obtained from formalin-fixed paraffin-embedded blocks, and expression of the targeted genes was quantified using a real time PCR approach. Linear regression analysis was performed to assess association between BMI and prostate volume adjusting for demographic characteristics and co-morbidity. Spearman’s correlation was used to examine whether gene expression was correlated with BMI, prostate volume, and age at surgery. Results A total of 278 patients were identified, including 62.9% European Americans (n = 175) and 27.7% Hispanic Americans (n = 77). BMI was significantly correlated with prostate volume (Spearman’s rho = 0.123, P = 0.045). In linear regression analysis, BMI was positively associated with prostate volume (β = 0.01, P = 0.004), while hyperlipidemia was negatively associated with prostate volume (β = −0.08, P = 0.02). A trend for a positive association was also observed for diabetes (β = 0.07, P = 0.099). In the race/ethnicity stratified analysis, age at surgery showed a trend for significantly positive association with prostate volume in European Americans (β = 0.005, P = 0.08), but not in Hispanic Americans. Expression of the A2M gene in the stroma was negatively correlated with age at surgery (P = 0.006). A2M expression in the gland was positively correlated with prostate volume among older men (Age ≥ 70, P = 0.01) and overweight men (BMI 25–30, P = 0.04). TGFB3 expression in the gland was positively correlated with BMI (P = 0.007) among older men. Conclusions This study demonstrated the positive correlation between BMI and prostate volume. Expression of TGFB3 and A2M was correlated with BMI, prostate volume, and age at surgery.

Red blood cell (RBC) transfusion remains a critical therapeutic intervention in sickle cell disease (SCD); however, the apparent propensity of some patients to regularly develop RBC alloantibodies after transfusion presents a significant challenge to finding compatible blood for so-called alloimmunization responders. Predisposing genetic loci have long been thought to contribute to the responder phenomenon, but to date, no definitive loci have been identified. We undertook a genome-wide association study of alloimmunization responder status in 267 SCD multiple transfusion recipients, using genetic estimates of ancestral admixture to bolster our findings. Analyses revealed single nucleotide polymorphisms (SNPs) on chromosomes 2 and 5 approaching genome-wide significance (minimum P = 2.0 × 10−8 and 8.4 × 10−8, respectively), with local ancestry analysis demonstrating similar levels of admixture in responders and nonresponders at implicated loci. Association at chromosome 5 was nominally replicated in an independent cohort of 130 SCD transfusion recipients, with meta-analysis surpassing genome-wide significance (rs75853687, Pmeta = 6.6 × 10−9), and this extended to individuals forming multiple (>3) alloantibodies (Pmeta = 9.4 × 10−5). The associated variant is rare outside of African populations, and orthogonal genome-wide haplotype analyses, contingent on local ancestry, revealed genome-wide significant sharing of a ∼60-kb haplotype of African ancestry at the chromosome 5 locus (Bayes Factor = 4.95). This locus overlaps a putative cis-acting enhancer predicted to regulate transcription of ADRA1B and the lncRNA LINC01847, both members of larger ontologies associated with immune regulation. Our findings provide potential insights to the pathophysiology underlying the development of alloantibodies and implicate non-RBC ancestry-limited loci in the susceptibility to alloimmunization.

Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw P-value

Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)–related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes. Administering IL-18 to isolated mouse hearts resulted in VT originating from the right ventricle and further reduced Ito in SCD mouse cardiomyocytes. Sustained IL-18 inhibition via IL-18–binding protein resulted in decreased cardiac fibrosis and NF-κB phosphorylation, improved diastolic function, normalized electrical remodeling, and attenuated IL-18–mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMCs), and QTc was strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in patients who did not survive compared with those who did. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.

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 correlations between incidence rates of these two cancer types and 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.