Polygenic score for body mass index in relation to mortality among patients with renal cell cancer.

BACKGROUND: The association between body mass index (BMI) and mortality among individuals with renal cell cancer (RCC) is debated, with some observational studies suggesting a lower mortality associated with higher BMI. However, methodological issues such as confounding and reverse causation may bias these findings. Using BMI-associated genetic variants can avoid these biases and generate more valid estimates. METHODS: In this prospective cohort study, we included 1264 RCC patients (446 deaths) from the UK Biobank. We created a BMI polygenic score (PGS) based on 336 BMI-associated genetic variants. The association between the PGS and mortality (all-cause and RCC-specific) was evaluated by logistic regression (all RCC cases) and Cox regression (906 incident cases). For comparison, the associations of measured pre-diagnostic BMI and waist-to-hip ratio (WHR) with mortality were quantified by Cox regression among incident cases. We stratified these analyses by time between anthropometric measurement and RCC diagnosis to assess the influence of reverse causation. RESULTS: We did not observe an association between the BMI PGS and all-cause mortality among RCC patients (hazard ratio (HR) per SD increase = 0.98, 95% CI: 0.88,1.10). No association was found for pre-diagnostic BMI (HR per 5 kg/m2 increase = 0.93, 95% CI: 0.83,1.04) or WHR (HR per 0.1 increase = 0.97, 95% CI: 0.83,1.13) with mortality. In patients with anthropometrics measured within 2 years before RCC diagnosis, we observed associations of higher BMI (HR per 5 kg/m2 = 0.76, 95% CI: 0.59,0.98) and WHR (HR = 0.67 per 0.1 increase, 95% CI: 0.45,0.98) with a lower risk of death. Similar patterns were observed for RCC-specific mortality. CONCLUSION: We found no association between either genetic variants for high BMI or measured pre-diagnostic body adiposity and mortality among RCC patients, and our results suggested a role for reverse causation in the association of obesity with lower mortality. Future studies should be designed carefully to produce unbiased estimates that account for confounding and reverse causation.

Best predictive single nephrometry score component to correlate with achievement of trifecta outcome in laparoscopic and robotic surgery.

BACKGROUND: To evaluate the predictive value of individual components of the R.E.N.A.L scoring system for Laparoscopic (LPN) and Robotic Partial Nephrectomy (RPN). METHODS: Patients that had undergone a Laparoscopic (LPN) or Robotic Partial Nephrectomy (RPN) between 2018 and 2023 were reviewed. Our data collection included Race, Ethnicity, Age, BMI, R.E.N.A.L nephrometry score, and complications. Cases that achieved trifecta outcomes were designated as "Group A" and cases that did not achieve trifecta were "Group B". All the data were collected using REDCap database. RESULTS: A total of 111 cases were included, Group A consisted of 82% of all cases, whereas Group B 18%. Radius score demonstrated significant distinction concerning trifecta attainment and was the most predictive component of the 5 scoring metrics of the nephrometry system. In a subgroup analysis, R-score of 3 or a renal mass measuring ≥ 7 cm, was a significant independent negative predictor for trifecta outcomes, as well as tumor size at presentation. CONCLUSION: Renal nephrometry score is predictive of trifecta outcomes for patients undergoing laparoscopic or robotic partial nephrectomy. Radius of mass was the most effective predictive component of the nephrometry score for trifecta prediction.

Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency.

A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10-30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04-1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias.

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.

Effect Modification of Selenium Supplementation by Intake and Serum Concentrations of Antioxidants on the Development of Metachronous Colorectal Adenoma.

BACKGROUND: Selenium (Se) is a trace element that has been investigated as a potential chemopreventive agent for colorectal cancer. Dietary intake of other antioxidant nutrients may modify the effect of Se. OBJECTIVE: We examined the association between intake and serum concentrations of retinol, ß-carotene, ß-cryptoxanthin, lycopene, lutein/zeaxanthin, and α- and γ-tocopherol and the development of metachronous colorectal adenoma, and if these nutrients modified the effect of Se. METHODS: We conducted a prospective study of 1874 participants from the Se Trial with data for antioxidant intake, as well as a subcohort of 508 participants with serum biomarker concentrations. RESULTS: Statistically significantly lower odds for the development of metachronous adenoma were observed for those participants in the highest tertile of intake for lutein/zeaxanthin compared to the lowest, with an OR (95% CI) of 0.72 (0.56-0.94). No effect modification for intake of any nutrient was observed. However, circulating concentrations of lycopene exhibited statistically significant effect modification of selenium supplementation (p < 0.06). CONCLUSION: These findings show that intake and circulating concentrations of antioxidant nutrients were not consistently associated with reduced odds for the development of metachronous lesions, although blood concentrations of lycopene may modify the effect of selenium supplementation.

Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial.

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 FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10-6) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10-6) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/ß-catenin pathway leading to colorectal neoplasia.Trial Registration number: NCT00078897 (ClinicalTrials.gov).

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

BACKGROUND: Inflammation 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. METHODS: We 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. RESULTS: We 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). CONCLUSION: Adverse events were consistent with the known safety profile of tocilizumab. Tocilizumab did not show any consistent treatment effect.

Factors Associated with Cancer Screening Among Hopi Men.

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 1 year ago. Among men who reported a colonoscopy, 60.8% had colonoscopy within the past 3 years. Similarly, among men who reported having had PSA, 72.3% had PSA within the past 3 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 (< 65) was associated with reduced odds of ever having prostate cancer screening (OR 0.28, 95% CI: 0.10-0.77). Ever having colorectal cancer screening and previous diagnosis of cancer increased odds of ever having prostate cancer screening (OR 3.15, 95% CI: 1.13-8.81 and OR 5.28, 95% CI: 1.15-24.18 respectively). This study illustrates the importance of community cancer education for men to improve cancer screening participation.

Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent.

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.

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.

Correlation between body mass index and prostate volume in benign prostatic hyperplasia patients undergoing holmium enucleation of the prostate surgery.

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 (ß = 0.01, P = 0.004), while hyperlipidemia was negatively associated with prostate volume (ß = -0.08, P = 0.02). A trend for a positive association was also observed for diabetes (ß = 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 (ß = 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.

Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension.

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.

Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor.

RATIONALE: Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches. OBJECTIVES: To identify genetic susceptibility targets for ARDS. METHODS: A genome-wide association study was performed on 232 African American patients with ARDS and 162 at-risk control subjects. The Identify Candidate Causal SNPs and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs. Preclinical validation of SELPLG (selectin P ligand gene) was performed using mouse models of LPS- and ventilator-induced lung injury. Exonic variation within SELPLG distinguishing patients with ARDS from sepsis control subjects was confirmed in an independent cohort. MEASUREMENTS AND MAIN RESULTS: Pathway prioritization analysis identified a nonsynonymous coding SNP (rs2228315) within SELPLG, encoding P-selectin glycoprotein ligand 1, to be associated with increased susceptibility. In an independent cohort, two exonic SELPLG SNPs were significantly associated with ARDS susceptibility. Additional support for SELPLG as an ARDS candidate gene was derived from preclinical ARDS models where SELPLG gene expression in lung tissues was significantly increased in both ventilator-induced (twofold increase) and LPS-induced (5.7-fold increase) murine lung injury models compared with controls. Furthermore, Selplg-/- mice exhibited significantly reduced LPS-induced inflammatory lung injury compared with wild-type C57/B6 mice. Finally, an antibody that neutralizes P-selectin glycoprotein ligand 1 significantly attenuated LPS-induced lung inflammation. CONCLUSIONS: These findings identify SELPLG as a novel ARDS susceptibility gene among individuals of European and African descent.

Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes.

Background: Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation. Objective: We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation. Methods: We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests. Results: Mean ± SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6 ± 28.9 and 138.7 ± 27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend = 0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of ß-cryptoxanthin (P-trend = 0.03) and lycopene (P-trend = 0.008); however, interaction terms were not significant. Conclusions: These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.

Race and BMI modify associations of calcium and vitamin D intake with prostate cancer.

BACKGROUND: African Americans have disproportionately higher burden of prostate cancer compared to European Americans. However, the cause of prostate cancer disparities is still unclear. Several roles have been proposed for calcium and vitamin D in prostate cancer pathogenesis and progression, but epidemiologic studies have been conducted mainly in European descent populations. Here we investigated the association of calcium and vitamin D intake with prostate cancer in multiethnic samples. METHODS: A total of 1,657 prostate cancer patients who underwent screening and healthy controls (888 African Americans, 620 European Americans, 111 Hispanic Americans, and 38 others) from Chicago, IL and Washington, D.C. were included in this study. Calcium and vitamin D intake were evaluated using food frequency questionnaire. We performed unconditional logistic regression analyses adjusting for relevant variables. RESULTS: In the pooled data set, high calcium intake was significantly associated with higher odds for aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 1.98, 95% C.I.: 1.01-3.91), while high vitamin D intake was associated with lower odds of aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 0.38, 95% C.I.: 0.18-0.79). In African Americans, the association between high calcium intake and aggressive prostate cancer was statistically significant (ORQuartile 1 vs. Quartile 4 = 4.28, 95% C.I.: 1.70-10.80). We also observed a strong inverse association between total vitamin D intake and prostate cancer in African Americans (ORQuartile 1 vs. Quartile 4 = 0.06, 95% C.I.: 0.02-0.54). In European Americas, we did not observe any significant associations between either calcium or vitamin D intake and prostate cancer. In analyses stratifying participants based on Body Mass Index (BMI), we observed a strong positive association between calcium and aggressive prostate cancer and a strong inverse association between vitamin D intake and aggressive prostate cancer among men with low BMI (<27.8 kg/m2), but not among men with high BMI (≥27.8 kg/m2). Interactions of race and BMI with vitamin D intake were significant (P Interaction < 0.05). CONCLUSION: Calcium intake was positively associated with aggressive prostate cancer, while vitamin D intake exhibited an inverse relationship. However, these associations varied by race/ethnicity and BMI. The findings from this study may help develop better prostate cancer prevention and management strategies.

Common vitamin D pathway gene variants reveal contrasting effects on serum vitamin D levels in African Americans and European Americans.

Vitamin D deficiency is more common among African Americans (AAs) than among European Americans (EAs), and epidemiologic evidence links vitamin D status to many health outcomes. Two genome-wide association studies (GWAS) in European populations identified vitamin D pathway gene single-nucleotide polymorphisms (SNPs) associated with serum vitamin D [25(OH)D] levels, but a few of these SNPs have been replicated in AAs. Here, we investigated the associations of 39 SNPs in vitamin D pathway genes, including 19 GWAS-identified SNPs, with serum 25(OH)D concentrations in 652 AAs and 405 EAs. Linear and logistic regression analyses were performed adjusting for relevant environmental and biological factors. The pattern of SNP associations was distinct between AAs and EAs. In AAs, six GWAS-identified SNPs in GC, CYP2R1, and DHCR7/NADSYN1 were replicated, while nine GWAS SNPs in GC and CYP2R1 were replicated in EAs. A CYP2R1 SNP, rs12794714, exhibited the strongest signal of association in AAs. In EAs, however, a different CYP2R1 SNP, rs1993116, was the most strongly associated. Our models, which take into account genetic and environmental variables, accounted for 20 and 28 % of the variance in serum vitamin D levels in AAs and EAs, respectively.

Mitochondrial variation among the Aymara and the signatures of population expansion in the central Andes.

OBJECTIVES: The exploitation of marine resources and intensive agriculture led to a marked population increase early in central Andean prehistory. Constant historic and prehistoric population movements also characterize this region. These features undoubtedly affected regional genetic variation, but the exact nature of these effects remains uncertain. METHODS: Mitochondrial DNA (mtDNA) hypervariable region I sequence variation in 61 Aymara individuals from La Paz, Bolivia, was analyzed and compared to sequences from 47 other South American populations to test hypotheses of whether increased female effective population size and gene flow influenced the mtDNA variation among central Andean populations. RESULTS: The Aymara and Quechua were genetically diverse showing evidence of population expansion and large effective population size, and a demographic expansion model fits the mtDNA variation found among central Andean populations well. Estimated migration rates and the results of AMOVA and multidimensional scaling analysis suggest that female gene flow was also an important factor, influencing genetic variation among the central Andeans as well as lowland populations from western South America. mtDNA variation in south central Andes correlated better with geographic proximity than with language, and fit a population continuity model. CONCLUSION: The mtDNA data suggests that the central Andeans experienced population expansion, most likely because of rapid demographic expansion after introduction of intensive agriculture, but roles of female gene flow need to be further explored.

Types of Racism and Health Disparities and Inequalities among Cancer Patients: An Editorial Reflection of Articles in This Special Issue of IJERPH.

Racism has been a long-standing influential factor that has negatively impacted both past and current health disparities within the United Sates population. Existing problems of racism and its impact on both health disparities and health inequalities were only amplified during the COVID-19 pandemic. The pandemic allowed both clinicians and researchers to recognize a growing list of health concerns at the macro-, meso-, and micro-level among underserved racially minoritized patients with specific chronic illnesses such as cancer. Based on these concerns, this Special Issue was designed to highlight the challenges of cancer screening, cancer treatment, and cancer-centered educational outreach among racially minoritized communities.

Prostate Cancer Disparities in Metastatic and Treatment Status for Hispanic Americans Based on Country of Origin Compared to Non-Hispanic Whites Using the National Cancer Database.

INTRODUCTION: Among Hispanic-American (HA) men, prostatic cancer (PCa) accounts for nearly one-quarter of the total cancer burden. We sought to identify differences in PCa presentation and treatment status for HA subgroups based on country/region of origin. MATERIAL AND METHODS: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA level at diagnosis from 2010 to 2016. HAs were divided into 4 subgroups: Mexican, Puerto Ricans, Cubans, and Central/South Americans. Non-Hispanic White (NHW) men were used as a reference group. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Models were constructed to evaluate the association of Hispanic country of origin with metastatic presentation and treatment status. RESULTS: A total of 428,829 patients were included, with 5625 (1.3%) classified as HA. Within the Hispanic group, 2880 (51.2%) were Mexican, 999 (17.8%) Puerto Rican, 477 (8.5%) Cuban, and 1269 (22.6%) South/Central American. Mexican men presented with higher median PSA, more Gleason 8 to 10 disease, and higher rates of metastatic presentation compared to NHW and other HA subgroups (all, p < .01). Metastatic rates over the study period for Mexican, Puerto Rican, Cuban, and South/Central Americans were 6.4 (±1.2), 5.3 (±3.0), 3.2 (±2.0), and 4.6% (±1.7), respectively (p = .01). Treatment rates were 89.1, 89.6, 92.4, and 89.3% for Mexican, Puerto Rican, Cuban, and South/Central Americans, respectively (p = .19). Mexican men had higher odds of initial metastatic presentation (OR: 1.32; 95%CI: 1.07-1.63, p = .01) but lower odds of receiving treatment (0.68; 0.55-0.85, p < .01). CONCLUSION: Men of Mexican origin presented with more advanced PCa when compared to NHW and other Hispanic subgroups. Our results warrant further investigation into potential biological factors affecting Hispanic patients as well as the identification of treatment barriers for this vulnerable population.

Disparities in hepatocellular carcinoma incidence among Hispanic and non-Hispanic adults in Arizona: Trends between 2009-2017.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer with few treatment options available to patients. Most HCC cases in Arizona, a state with a high proportion of Hispanic adults, have not been included in recent reports of HCC incidence. This study describes trends in HCC incidence and stage at diagnosis among Arizona residents between 2009-2017 and reports on racial and ethnic disparities for these outcomes. METHODS: The Arizona Cancer Registry was used to identify Arizonans aged 19 or older diagnosed with liver cell carcinoma diagnosed between 2009-2017. A total of 5043 cases were examined. Adjusted annual and 3-year HCC incidence rates (per 100,000) were examined for non-Hispanic White (NHW) and Hispanic adults. RESULTS: The total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017. CONCLUSION: Whe total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017.