Publications by authors named "Rick Kittles"

Few biological or clinical predictors guide medication selection and/or dosing for attention-deficit/hyperactivity disorder (ADHD). Accumulating data suggest that genetic factors may contribute to clinically relevant pharmacodynamic (e.g.

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Importance: Racial disparities in prostate cancer are likely the result of complex relationships between both socioeconomic and environmental factors captured by the neighborhood environment and genetic factors, including West African genetic ancestry. However, few studies have examined the combined role of neighborhood environment and genetic ancestry in developing lethal prostate cancer.

Objective: To examine the interactions between West African genetic ancestry and neighborhood deprivation in modifying prostate cancer risk and mortality.

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Article Synopsis
  • - Bladder cancer mortality rates are higher in African American (AA) patients compared to European American (EA) patients, but the reasons for this disparity are not fully understood.
  • - Research using RNA-Seq, proteomics, and metabolomics shows that AA bladder cancer has increased mitochondrial oxidative phosphorylation (OXPHOS) driven by complex I activation, leading to metabolic changes that promote disease progression.
  • - Targeting components of complex I and the enzyme GLS1 could be a potential therapeutic strategy, as knocking down these factors reduced tumor growth and mitochondrial activity in AA bladder cancer cells.
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Unlabelled: Prostate cancer is the second leading cause of death for men in the U.S. and Black men are twice as likely to die from the disease.

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Background: In the United States, Black men are at highest risk for being diagnosed with and dying from prostate cancer. Given this disparity, we examined relevant data to establish clinical prostate-specific antigen (PSA) screening guidelines for Black men in the United States.

Methods: A comprehensive literature search identified 1848 unique publications for screening.

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Vitamin D is a steroid hormone that confers anti-tumorigenic properties in prostate cells. Serum vitamin D deficiency has been associated with advanced prostate cancer (PCa), particularly affecting African American (AA) men. Therefore, elucidating the pleiotropic effects of vitamin D on signaling pathways, essential to maintaining non-malignancy, may provide additional drug targets to mitigate disparate outcomes for men with PCa, especially AA men.

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Article Synopsis
  • - Health equity means everyone has equal chances to achieve their best health, but human genomics research has not reflected the diversity of the population, leading to health disparities.
  • - The National Human Genome Research Institute (NHGRI) acknowledges these inequities and has gathered experts to provide recommendations and review the current state of health equity in genomics.
  • - This report outlines the gaps and opportunities in bridging human genomics with health equity, emphasizing the need for more diverse participation in genomics research to improve health outcomes for all.
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Background: A limited pool of SNPs are linked to the development and severity of sarcoidosis, a systemic granulomatous inflammatory disease. By integrating genome-wide association studies (GWAS) data and expression quantitative trait loci (eQTL) single nuclear polymorphisms (SNPs), we aimed to identify novel sarcoidosis SNPs potentially influencing the development of complicated sarcoidosis.

Methods: A GWAS (Affymetrix 6.

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Prostate cancer is the second most commonly diagnosed non-skin malignancy and the second leading cause of cancer death among men in the USA. However, the mortality rate of African American men aged 40-60 years is almost 2.5-fold greater than that of European American men.

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Introduction: Social determinants of health (SDOH) are non-clinical factors that may affect the outcomes of cancer patients. The purpose of this study was to describe the influence of SDOH factors on quality of life (QOL)-related outcomes for lung cancer surgery patients.

Methods: Thirteen patients enrolled in a randomized trial of a dyadic self-management intervention were invited and agreed to participate in semi-structured key informant interviews at study completion (3 months post-discharge).

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Prostate cancer (PCa) in African American men is one of the most common cancers with a great disparity in outcomes. The higher incidence and tendency to present with more advanced disease have prompted investigators to postulate that this is a problem of innate biology. However, unequal access to health care and poorer quality of care raise questions about the relative importance of genetics versus social/health injustice.

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Article Synopsis
  • A recent study analyzed genetic data from over 156,000 prostate cancer cases and 788,000 controls from diverse populations, significantly increasing the representation of non-European participants.
  • Researchers identified 187 new genetic risk variants for prostate cancer, bringing the total to 451, enhancing understanding of genetic factors across different ancestries.
  • The developed genetic risk score (GRS) showed varying risk levels for prostate cancer among different ancestry groups, highlighting its potential for better risk assessment, especially in men of African descent.
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Purpose: We sought to develop and validate a prostate biopsy risk calculator for Black men and compare it with the Prostate Cancer Prevention Trial version 2.0, Prostate Biopsy Collaborative Group, and Kaiser Permanente Prostate Cancer Risk Calculators for the detection of Gleason Grade Group (GG) ≥ 2 prostate cancer (PCa).

Materials And Methods: We prospectively recruited 2 cohorts of men undergoing prostate biopsy from 5 facilities in Chicago.

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Multiple sclerosis is an inflammatory degenerative condition of the central nervous system that may result in debilitating disability. Several studies over the past twenty years suggest that multiple sclerosis manifests with a rapid, more disabling disease course among individuals identifying with Black or Latin American ethnicity relative to those of White ethnicity. However, very little is known about immunologic underpinnings that may contribute to this ethnicity-associated discordant clinical severity.

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Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS.

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Article Synopsis
  • Genome-wide polygenic risk scores (GW-PRS) were analyzed for their predictive ability regarding prostate cancer risk, compared to an established multi-ancestry polygenic risk score (PRS).
  • The GW-PRS models utilized data from a large and diverse group of nearly 235,000 participants, including individuals from both African and European ancestries.
  • Results showed that while GW-PRS had varying predictive abilities, the multi-ancestry PRS performed equally well or better in predicting prostate cancer risk for both ancestry groups, indicating GW-PRS may not offer significant improvements in risk prediction.
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Pulmonary hypertension (PH) is associated with significant morbidity and mortality. RASA3 is a GTPase activating protein integral to angiogenesis and endothelial barrier function. In this study, we explore the association of RASA3 genetic variation with PH risk in patients with sickle cell disease (SCD)-associated PH and pulmonary arterial hypertension (PAH).

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Unlabelled: African American (AA) prostate cancer associates with vitamin D deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex.

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Unlabelled: Vitamin D deficiency is associated with an increased risk of prostate cancer mortality and is hypothesized to contribute to prostate cancer aggressiveness and disparities in African American populations. The prostate epithelium was recently shown to express megalin, an endocytic receptor that internalizes circulating globulin-bound hormones, which suggests regulation of intracellular prostate hormone levels. This contrasts with passive diffusion of hormones that is posited by the free hormone hypothesis.

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Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

Design, Setting, And Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

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Dihydrotestosterone (DHT) and testosterone (T), which mediate androgen receptor nuclear translocation and target gene transcription, are crucial androgens and essential molecular triggers required for the proliferation and survival of prostate cancer cells. Therefore, androgen metabolism is commonly targeted in the treatment of prostate cancer. Using a high-pressure liquid chromatographic assay with tandem mass spectral detection, we determined the serum levels of metabolites produced during DHT/T biosynthesis in African American (AA) and European American (EA) men with localized, therapy naïve prostate cancer.

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Purpose: Vitamin D metabolites may be protective against prostate cancer (PCa). We conducted a cross-sectional analysis to evaluate associations between in vivo vitamin D status, genetic ancestry, and degree of apoptosis using prostatic epithelial terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.

Experimental Design: Benign and tumor epithelial punch biopsies of participants with clinically localized PCa underwent indirect TUNEL staining.

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Many advanced cancer models, such as patient-derived xenografts (PDXs), offer significant benefits in their preservation of the native tumor's heterogeneity and susceptibility to treatments, but face significant barriers to use in their reliance on a rodent host for propagation and screening. PDXs remain difficult to implement in vitro, particularly in configurations that enable both detailed cellular analysis and high-throughput screening (HTS). Complex multilineage co-cultures with stromal fibroblasts, endothelium, and other cellular and structural components of the tumor microenvironment (TME) further complicate ex vivo implementation.

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