Vitamin D receptor polymorphisms and associated miRNAs in the development of breast cancer in African American women.

Breast cancer (BCa) is a prevalent form of cancer in women, exhibiting varying rates and distribution across different ethnic groups. Among these groups, African American (AA) women have the highest incidence of BCa and the lowest levels of Vitamin D (VD). Numerous studies have explored the connection between variations in the VDR gene and BCa risk, particularly in different populations, but research on the AA population remains limited.

Cyclin A2 and Ki-67 proliferation markers could be used to identify tumors with poor prognosis in African American women with breast cancer.

Background: Diagnosed invasive breast carcinomas in African American patients are more aggressive compared with those in Caucasian patients and diagnosed at later stages of the disease with higher grade tumors. Despite advances in breast cancer systemic treatment, new prognostic and predictive biomarkers are still needed. Therefore, potential biomarkers were chosen to correlate with different subtypes, recurrence, and survival of invasive breast cancer in a cohort of African American women.

Sex differences in saliva-based DNA methylation changes and environmental stressor in young African American adults.

Background: Low socioeconomic status neighborhood exposure to stress and violence may be sources of negative stimuli that poses significant health risks for children, adolescents and throughout the life course of an individual. The study aims to investigate if aberrant epigenetic DNA methylation changes may be a potential mechanism for regulating neighborhood exposures and health outcomes.

Methods: Exposure to environmental stressors identified in 98 young African American (AA) adults aged 18-25 years old from the Washington D.

A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer.

Background: To investigate the global expression profile of miRNAs, their impact on cellular signaling pathways, and their association with poor prognostic parameters in African-American (AA) patients with triple negative breast cancer (TNBC).

Methods: Twenty-five samples of AA TNBC patients were profiled for global miRNA expression and stratified considering three clinical-pathological parameters: tumor size, lymph node (LN), and recurrence (REC) status. Differential miRNA expression analysis was performed for each parameter, and their discriminatory power was determined by Receiver Operating Characteristic (ROC) curve analysis.

The Association Between the Genetic SNP c.907+75C>T and Prostate Cancer Risk Is Modified by Tanning Potential.

Background: Prostate cancer (PCa) is a multifactorial disease involving complex interactions between genetic and physiological/environmental factors. Vitamin D receptor (VDR) plays a role in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to PCa.

Materials And Methods: Logistic regression analysis was used to assess the association of six VDR single nucleotide polymorphisms (SNPs) and factors such as tanning potential and UV sunlight exposure with PCa risk.

Significant Quantitative Differences in Orexin Neuronal Activation After Pain Assessments in an Animal Model of Sickle Cell Disease.

Sickle cell disease is a hemoglobinopathy that causes sickling of red blood cells, resulting in vessel blockage, stroke, anemia, inflammation, and extreme pain. The development and treatment of pain, in particular, neuropathic pain in sickle cell disease patients is poorly understood and impedes our progress toward the development of novel therapies to treat pain associated with sickle cell disease. The orexin/hypocretin system offers a novel approach to treat chronic pain and hyperalgesia.

Genetic Polymorphisms in IL-10 Promoter Are Associated With Smoking and Prostate Cancer Risk in African Americans.

Background/aim: Even though prostate cancer (PCa) has good prognosis, there is a discrepancy in the risk among ethnic groups, with high morbidity in African American men. Single nucleotide polymorphisms (SNPs) in interleukin 10 (IL-10) have been associated with inflammation and cancer risk. We investigated the association of five SNPs in the IL-10 promoter with clinical features such as Gleason score and smoking.

Association of Genetic Ancestry With DNA Methylation Changes in Prostate Cancer Disparity.

Background: We hypothesized that ancestry-mediated methylated DNA changes may drive racial and ethnic disparity in prostate cancer (PCa). To test this hypothesis, we analyzed genetic ancestry and association with DNA methylation changes in PCa disparity.

Materials And Methods: Pyrosequencing and ancestry informative markers were used for DNA methylation and genetic ancestry testing, respectively.

The Association of a Novel Identified SNP With Prostate Cancer in African American Men.

Background/aim: Vitamin D receptor (VDR) is present in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to prostate cancer. Also, analyses of single nucleotide polymorphisms (SNPs) in VDR revealed ethnicity-associated polymorphisms. The aim of this study was to identify VDR SNPs in African American men with and without prostate cancer.

Correlating blood-based DNA methylation markers and prostate cancer risk in African-American men.

The objective of this work was to investigate the clinical significance of promoter gene DNA methylation changes in whole blood from African-American (AA) men with prostate cancer (PCa). We used high throughput pyrosequencing analysis to quantify percentage DNA methylation levels in a panel of 8 genes (RARβ2, TIMP3, SPARC, CDH13, HIN1, LINE1, CYB5R2 and DRD2) in blood DNA obtained from PCa and non-cancerous controls cases. Correlations of methylation status and various clinicopathological features were evaluated.

Modeling clustered binary data with excess zero clusters.

We establish a zero-inflated (random-effects) logistic-Gaussian model for clustered binary data in which members of clusters in one latent class have a zero response with probability one, and members of clusters in a second latent class yield correlated outcomes. Response probabilities in terms of random-effects models are formulated, and maximum marginal likelihood estimation procedures based on Gaussian quadrature are developed. Application to esophageal cancer data in Chinese families is presented.

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.

Background: Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa.

Method: We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9-10 (WHO5).

DHPLC Elution Patterns of PCR Products Can Predict Prostate Cancer Susceptibility in African American Men.

Background/aim: Denaturing high-performance liquid chromatography (DHPLC) is a technique that is used to detect mutations. The aim of the present study was to determine whether DHPLC elution patterns of vitamin D receptor (VDR) gene PCR products can serve as indicators of susceptibility to prostate cancer (PCa) risk.

Materials And Methods: DNA samples of PCa cases and controls were screened for mutations and/or polymorphisms in coding exons of VDR gene using DHPLC analysis.

Analysis of Incomplete Longitudinal Binary Data-A Combined Markov's Transition and Logistic Model for Non-ignorable Missingness.

The problem of incomplete data is a common phenomenon in research that involves the longitudinal design approach. We investigate and develop a likelihood-based approach for incomplete longitudinal binary data using the disposition model when the missing value mechanism is non-ignorable. We combined Markov's transition and a logistic regression model to build the dropout process and model the response using conditional logistic regression model.

A Correlated Binary Model for Ignorable Missing Data: Application to Rheumatoid Arthritis Clinical Data.

Incomplete data are common phenomenon in research that adopts the longitudinal design approach. If incomplete observations are present in the longitudinal data structure, ignoring it could lead to bias in statistical inference and interpretation. We adopt the disposition model and extend it to the analysis of longitudinal binary outcomes in the presence of monotone incomplete data.

Genetic Polymorphisms of TLR4 and MICA are Associated with Severity of Trachoma Disease in Tanzania.

Aim: To examine the association of TLR4 Asp299Gly and MICA exon 5 microsatellites polymorphisms with severity of trachoma in a sub-Saharan East Africa population of Tanzanian villagers.

Methods: The samples were genotyped for MICA exon 5 microsatellites and the TLR4 299 A/G polymorphism by Restriction Fragment Length Polymorphism (RFLP), and GeneScan, respectively. The association of TLR4 Asp299Gly and MICA exon 5 microsatellites with inflammatory trachoma (TI) and trichiasis (TI) were examined.

Use of tanning potential as a predictor for prostate cancer risk in African-American men.

Background/aim: Vitamin D deficiency in African-Americans is common due to the high melanin content of the skin that reduces the absorption of UV radiation. To determine if there is a correlation between UV exposure, tanning potential and vitamin D with prostate cancer (PC) risk, we conducted a case-control study of 183 African-American men aged 40 years and older residing in the Washington, DC area.

Patients And Methods: PC status was described as a binary variable as the presence or absence of cancer and the environmental factors as continuous variables.

Linkage disequilibrium and haplotype analysis of COX-2 and risk of colorectal adenoma development.

Single nucleotide polymorphisms (SNPs) in the promoter and untranslated region of cyclooxygenase (COX)-2, an inducible enzyme responsible for the synthesis of prostaglandins, have been reported to modulate the risk for many human cancers. We performed comprehensive linkage disequilibrium (LD) and haplotype analyses of 13 single nucleotide polymorphisms of the COX-2 gene and examined its susceptibility to adenoma development in 72 African American cases and 142 controls. Results revealed significant variation in LD patterns with consequence for adenoma development.

Global pattern of pairwise relationship in genetic network.

In recent times genetic network analysis has been found to be useful in the study of gene-gene interactions, and the study of gene-gene correlations is a special analysis of the network. There are many methods for this goal. Most of the existing methods model the relationship between each gene and the set of genes under study.

Identification of differentially methylated genes in normal prostate tissues from African American and Caucasian men.

Purpose: Aberrant DNA methylation changes are common somatic alterations in prostate carcinogenesis. We examined the methylation status of six genes in prostate tissue specimens from African American (AA) and Caucasian (Cau) males.

Experimental Design: We used pyrosequencing to quantitatively measure the methylation status of GSTP1, AR, RARbeta2, SPARC, TIMP3, and NKX2-5.

Association of CD14 variant with prostate cancer in African American men.

Background: African American men have the highest rates of prostate cancer worldwide, and immunogenetic studies suggest that people of African descent have increased susceptibility to diseases of inflammation. Since genetic susceptibility is an etiological factor in prostate cancer, we hypothesize that sequence variants in the promoter region of the CD14 gene that regulate inflammation may modify individual susceptibility to this disease.

Methods: The CD14 promoter was screened for single-nucleotide polymorphisms (SNPs) using dHPLC.

The Howard University Hospital experience with routineized HIV screening: a progress report.

Background: Howard University Hospital (HUH) is the first hospital in the nation to have instituted a hospital-wide routine rapid HIV screening campaign as recommended by the CDC for healthcare settings.

Methods: HUH developed a protocol and implemented a hospital-wide routine HIV screening in October 2006. Rapid oral fluid-based HIV testing was conducted throughout the hospital using the OraSure OraQuick Advance Rapid HIV-1/2 Antibody Test.

Human leukocyte antigen (HLA)-B, DRB1, and DQB1 allotypes associated with disease and protection of trachoma endemic villagers.

Purpose: Trachoma remains the leading preventable infectious cause of blindness in developing countries. Human leukocyte antigen (HLA) associations with ocular disease severity and persistent Chlamydia trachomatis infection of Tanzanians living in trachoma-endemic villages were examined to determine possible protective candidate allotypes for vaccine development.

Methods: Buccal swab scrapes were taken from subjects in the Trichiasis Study Group (TSG), which studied females only, and the Family Trachoma Study (FTS), which compared persistently infected probands who had severe disease with disease-free siblings and parents.

Using linkage and association to identify and model genetic effects: summary of GAW15 Group 4.

Group 4 at Genetic Analysis Workshop 15 focused on methods that exploited both linkage and association information to map disease loci. All contributions considered the dichotomous trait of rheumatoid arthritis, using either affected sibpairs and/or unrelated controls. While one contribution investigated linkage and association approaches separately in genome-wide analyses, the remaining others focused on joint linkage and association methods in specific genomic regions.

An extension of the weighted dissimilarity test to association study in families.

Association studies for complex diseases based on pedigree haplotype or genotype data have received increasing attention in the last few years. The similarity tests are appealing for these studies because they take into account of the DNA structure, but they have blind areas on which significant association can not be detected. Recently, we developed a dissimilarity method for this problem based on independent haplotype data, which eliminates the blind areas of the existing methods.