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Health inequity drives disease biology to create disparities in prostate cancer outcomes.
Nelson, WG, Brawley, OW, Isaacs, WB, Platz, EA, Yegnasubramanian, S, Sfanos, KS, Lotan, TL, De Marzo, AM
The Journal of clinical investigation. 2022;(3)
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Abstract
Prostate cancer exerts a greater toll on African American men than on White men of European descent (hereafter referred to as European American men): the disparity in incidence and mortality is greater than that of any other common cancer. The disproportionate impact of prostate cancer on Black men has been attributed to the genetics of African ancestry, to diet and lifestyle risk factors, and to unequal access to quality health care. In this Review, all of these influences are considered in the context of the evolving understanding that chronic or recurrent inflammatory processes drive prostatic carcinogenesis. Studies of inherited susceptibility highlight the contributions of genes involved in prostate cell and tissue repair (BRCA1/2, ATM) and regeneration (HOXB13 and MYC). Social determinants of health appear to accentuate these genetic influences by fueling prostate inflammation and associated cell and genome damage. Molecular characterization of the prostate cancers that arise in Black versus White men further implicates this inflammatory microenvironment in disease behavior. Yet, when Black and White men with similar grade and stage of prostate cancer are treated equally, they exhibit equivalent outcomes. The central role of prostate inflammation in prostate cancer development and progression augments the impact of the social determinants of health on disease pathogenesis. And, when coupled with poorer access to high-quality treatment, these inequities result in a disparate burden of prostate cancer on African American men.
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Dysglycemia and Abnormal Adiposity Drivers of Cardiometabolic-Based Chronic Disease in the Czech Population: Biological, Behavioral, and Cultural/Social Determinants of Health.
Pavlovska, I, Polcrova, A, Mechanick, JI, Brož, J, Infante-Garcia, MM, Nieto-Martínez, R, Maranhao Neto, GA, Kunzova, S, Skladana, M, Novotny, JS, et al
Nutrients. 2021;(7)
Abstract
In contrast to the decreasing burden related to cardiovascular disease (CVD), the burden related to dysglycemia and adiposity complications is increasing in Czechia, and local drivers must be identified. A comprehensive literature review was performed to evaluate biological, behavioral, and environmental drivers of dysglycemia and abnormal adiposity in Czechia. Additionally, the structure of the Czech healthcare system was described. The prevalence of obesity in men and diabetes in both sexes has been increasing over the past 30 years. Possible reasons include the Eastern European eating pattern, high prevalence of physical inactivity and health illiteracy, education, and income-related health inequalities. Despite the advanced healthcare system based on the compulsory insurance model with free-for-service healthcare and a wide range of health-promoting initiatives, more effective strategies to tackle the adiposity/dysglycemia are needed. In conclusion, the disease burden related to dysglycemia and adiposity in Czechia remains high but is not translated into greater CVD. This discordant relationship likely depends more on other factors, such as improvements in dyslipidemia and hypertension control. A reconceptualization of abnormal adiposity and dysglycemia into a more actionable cardiometabolic-based chronic disease model is needed to improve the approach to these conditions. This review can serve as a platform to investigate causal mechanisms and secure effective management of cardiometabolic-based chronic disease.
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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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Characterization of the Asian Phenotype - An Emerging Paradigm with Clinicopathological and Human Research Implications.
Leow, MK
International journal of medical sciences. 2017;(7):639-647
Abstract
Background: Modern medicine recognizes that salient, inherent variations between Caucasians and Asians exist. Radical changes are occurring in the health scene with increasing emphasis centered on the recognition of inter-individual variations unique to Asians that impact on medical management and outcomes. Aim: This review analyzes distinct features or outcomes in terms of epidemiology, disease thresholds, diagnostic cutoffs and treatment responses of Asian people compared with non-Asians. Methods: This review is based on a literature search via PubMed and MEDLINE for relevant articles related to the Asian phenotype and its impact on health and disease. Results: An 'Asian phenotype' could be characterized across the spectrum of biomedical disciplines and underscores the major challenges clinicians must face in their daily management of a cosmopolitan population and their extrapolation of research outcomes. Conclusion: Interventions for various ailments that have traditionally ignored population differences have now entered the age of personalized, stratified or precision medicine requiring an individualized approach being adopted as a new standard of care. Factoring in Asian phenotypes is essential for the medical research community and the development of improved clinical practice guidelines across a continuum of disciplines that will ultimately translate to better human health round the world.
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Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis.
Guo, SX, Yao, MH, Ding, YS, Zhang, JY, Yan, YZ, Liu, JM, Zhang, M, Rui, DS, Niu, Q, He, J, et al
International journal of environmental research and public health. 2016;(9)
Abstract
BACKGROUND Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism (rs708272), the risk of developing composite ischemic cardiovascular disease (CVD) and the concentration of high-density lipoprotein cholesterol (HDL-C), but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. METHODS We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. RESULTS Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09-1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. RESULTS suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36-0.65, p < 0.001. CONCLUSIONS The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians.
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Biomarkers of Coronary Artery Disease Differ Between Asians and Caucasians in the General Population.
Gijsberts, CM, den Ruijter, HM, Asselbergs, FW, Chan, MY, de Kleijn, DP, Hoefer, IE
Global heart. 2015;(4):301-311.e11
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Abstract
Coronary artery disease (CAD) markers have not been thoroughly investigated among Asians. The incidence of CAD, however, is rising rapidly in Asia. In this review, we systematically discuss publications that compare CAD biomarkers between Asians and Caucasians in the general population. A PubMed search yielded 5,570 hits, containing 59 articles describing 47 unique cohorts that directly compare Asians with Caucasians. Ten biomarkers were taken into account for this review: total cholesterol; triglycerides; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; C-reactive protein; glucose; insulin; glycated hemoglobin; fibrinogen; and plasminogen activator inhibitor-1. Triglycerides were 1.13-fold higher in South Asians than in Caucasians, and insulin levels were 1.33-fold higher. In Japanese and Chinese subjects, lower C-reactive protein levels were reported: 0.52 and 0.36-fold, respectively. Ethnicity-specific prognostic measures of CAD biomarkers were rarely reported. CAD biomarker levels differ between Asians and Caucasians and among Asian ethnic groups in population-based cohorts. The ethnicity-specific prognostic value of CAD biomarkers is yet to be determined.
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Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: a case-control and meta-analysis study.
Phani, NM, Guddattu, V, Bellampalli, R, Seenappa, V, Adhikari, P, Nagri, SK, D Souza, SC, Mundyat, GP, Satyamoorthy, K, Rai, PS
PloS one. 2014;(9):e107021
Abstract
BACKGROUND AND OBJECTIVES Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis. METHODS A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies. RESULTS KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians. CONCLUSION KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.
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Population ancestry and genetic risk for diabetes and kidney, cardiovascular, and bone disease: modifiable environmental factors may produce the cures.
Freedman, BI, Divers, J, Palmer, ND
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2013;(6):1165-75
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Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This article provides evidence in support of differential allele frequency distributions that underlie the higher rates of nondiabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biological factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The present era of precision medicine will couple one's genetic makeup with specific therapies to reduce rates of disease based on the presence of disease-specific alleles.
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Phenotypes and genotypes of patients with pantothenate kinase-associated neurodegeneration in Asian and Caucasian populations: 2 cases and literature review.
Lee, CH, Lu, CS, Chuang, WL, Yeh, TH, Jung, SM, Huang, CL, Lai, SC
TheScientificWorldJournal. 2013;:860539
Abstract
OBJECTIVES Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disease caused by pantothenate kinase 2 (PANK2, OMIM 606157) mutations. This study is aimed to investigate clinical presentations, pathologies, and genetics in patients with PKAN. METHODS Two patients with PKAN were reported. We reviewed the literature to include additional 19 patients with PKAN in Eastern Asia. These patients were divided into classic and atypical groups by the age of onset. We compared the data on PKAN patients of Asian and Caucasian populations. RESULTS We found iron deposits in the globus pallidus in our Patient 1 and a heterozygous truncating mutation (c.1408insT) in Patient 2. Literature review shows that generalized dystonia and bulbar signs are more common in classic PKAN patients, whereas segmental dystonia and tremors are more specific to atypical ones. Asian patients have less complex presentations--lower prevalence of pyramidal signs, mental impairment, and parkinsonism--than Caucasians. D378G in exon 3 is the most frequent mutation (28%) in Asians. CONCLUSIONS Our study demonstrates that the distribution of dystonia is the major distinction between subgroups of PKAN. Caucasian patients have more complex presentations than Asians. Exon 3 and 4 are hot spots for screening PANK2 mutations in Asian patients.
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The pharmacogenetics of the response to warfarin in Chinese.
Lam, MP, Cheung, BM
British journal of clinical pharmacology. 2012;(3):340-7
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Warfarin is a commonly used oral anticoagulant with a narrow therapeutic range and large interindividual variability in daily dose. Compared with Caucasians, Chinese are known to require lower doses of warfarin. Differences between Caucasians and Chinese in the allelic frequencies of two genes, CYP2C9 and VKORC1, largely explain the difference in dose requirement. There are other genetic polymorphisms that may further explain the response to warfarin. The VKORC1 genotype is an important determinant of response to warfarin in Chinese, but some genetic variants found in other ethnic groups that have a large effect on warfarin response and dosing are not commonly found in Chinese. Therefore, it is important to recognize and beware of ethnic differences in the pharmacogenetics of the response to warfarin, especially in the design of algorithms to aid dosing in clinical practice.