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Racial disparity in prostate cancer in the African American population with actionable ideas and novel immunotherapies.
Dovey, ZS, Nair, SS, Chakravarty, D, Tewari, AK
Cancer reports (Hoboken, N.J.). 2021;(5):e1340
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Abstract
BACKGROUND African Americans (AAs) in the United States are known to have a higher incidence and mortality for Prostate Cancer (PCa). The drivers of this epidemiological disparity are multifactorial, including socioeconomic factors leading to lifestyle and dietary issues, healthcare access problems, and potentially tumor biology. RECENT FINDINGS Although recent evidence suggests once access is equal, AA men have equal outcomes to Caucasian American (CA) men, differences in PCa incidence remain, and there is much to do to reverse disparities in mortality across the USA. A deeper understanding of these issues, both at the clinical and molecular level, can facilitate improved outcomes in the AA population. This review first discusses PCa oncogenesis in the context of its diverse hallmarks before benchmarking key molecular and genomic differences for PCa in AA men that have emerged in the recent literature. Studies have emphasized the importance of tumor microenvironment that contributes to both the unequal cancer burden and differences in clinical outcome between the races. Management of comorbidities like obesity, hypertension, and diabetes will provide an essential means of reducing prostate cancer incidence in AA men. Although requiring further AA specific research, several new treatment strategies such as immune checkpoint inhibitors used in combination PARP inhibitors and other emerging vaccines, including Sipuleucel-T, have demonstrated some proven efficacy. CONCLUSION Genomic profiling to integrate clinical and genomic data for diagnosis, prognosis, and treatment will allow physicians to plan a "Precision Medicine" approach to AA men. There is a pressing need for further research for risk stratification, which may allow early identification of AA men with higher risk disease based on their unique clinical, genomic, and immunological profiles, which can then be mapped to appropriate clinical trials. Treatment options are outlined, with a concise description of recent work in AA specific populations, detailing several targeted therapies, including immunotherapy. Also, a summary of current clinical trials involving AA men is presented, and it is important that policies are adopted to ensure that AA men are actively recruited. Although it is encouraging that many of these explore the lifestyle and educational initiatives and therapeutic interventions, there is much still work to be done to reduce incidence and mortality in AA men and equalize current racial disparities.
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Vitamin D receptor ApaI, TaqI, BsmI, and FokI polymorphisms and psoriasis susceptibility: an updated meta-analysis.
Lee, YH
Clinical and experimental dermatology. 2019;(5):498-505
Abstract
BACKGROUND Vitamin D is considered a regulator of the immune system, and its polymorphisms have been associated with psoriasis in some but not all reports. AIM: To explore whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to psoriasis. METHODS Meta-analyses were conducted to determine the associations between psoriasis and the VDR ApaI, TaqI, BsmI and FokI polymorphisms in all participants, and stratified by ethnic group. RESULTS In total, 16 studies on VDR polymorphisms and psoriasis were included in this meta-analysis, which involved 2086 patients and 2182 controls. The meta-analysis indicated an association between psoriasis and the VDR TaqI TT genotype in Caucasian (OR = 1.29, 95% CI = 1.00-1.66, P < 0.05), but not in Asian (OR = 1.32, 95% CI = 0.89-1.96, P = 0.16) populations. However, no association was found between psoriasis and the VDR TaqI polymorphism using dominant, allele contrast or homozygous contrast models. No association was found between psoriasis and either the VDR ApaI, BsmI or FokI polymorphisms by meta-analyses of the allele contrast, recessive, or dominant models or homozygous contrast models in the overall, Caucasian or Asian populations. CONCLUSION This meta-analysis showed that polymorphisms in VDR ApaI, BsmI and FokI are not associated with psoriasis susceptibility in overall, Caucasian or Asian populations. However, the VDR TaqI polymorphism is associated with psoriasis susceptibility in Caucasian populations.
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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.
Jiang, X, O'Reilly, PF, Aschard, H, Hsu, YH, Richards, JB, Dupuis, J, Ingelsson, E, Karasik, D, Pilz, S, Berry, D, et al
Nature communications. 2018;(1):260
Abstract
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.
Cerhan, JR, Berndt, SI, Vijai, J, Ghesquières, H, McKay, J, Wang, SS, Wang, Z, Yeager, M, Conde, L, de Bakker, PI, et al
Nature genetics. 2014;(11):1233-8
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Abstract
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.