Molecular basis for prostate cancer racial disparities.
Ontology highlight
ABSTRACT:
SUBMITTER: Singh SK
PROVIDER: S-EPMC5550772 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
Publications
Molecular basis for prostate cancer racial disparities.
Singh Santosh K SK Lillard James W JW Singh Rajesh R
Frontiers in bioscience (Landmark edition) 20170101 3
Prostate cancer (PCa) remains the most common cancer in American men. African-American (AA) men continue to have higher PCa prevalence and mortality rates compared to men in other populations. In addition to socioeconomic factors and lifestyle differences, molecular alterations contribute to this discrepancy. We summarize molecular genetics research results interrelated with the biology of PCa racial disparity. Androgen and androgen receptor (AR) pathways have long been associated with prostate ...[more]
Similar Datasets
Project description:Prostate cancer incidence and mortality rates are remarkably higher in African-American men as compared to their European-Americans counterparts. Despite these recognitions, precise causes underlying such prevalent racial disparities remain poorly understood. Although socioeconomic factors could account for such differences up to a certain extent, it is now being increasingly realized that such disparity has a molecular basis. Indeed, several differences, including genetic polymorphism, gene mutations, epigenetic modifications, miRNAs alterations, etc., have been reported in malignant prostate tissues from patients of diverse racial backgrounds. Here, we attempt to provide a molecular perspective on prostate cancer racial disparities by gathering available information on these associated factors and discussing their potential significance in disproportionate incidence and clinical outcomes.
| S-EPMC5242333 | biostudies-literature
Project description:Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, race disparities persist. For African American men (AAM), PCa is more often an aggressive disease showing increased metastases and greater PCa-related mortality compared with European American men. The earliest research points to how distinctions are likely the result of a combination of factors, including ancestry genetics and lifestyle variables. More recent research considers that cancer, although influenced by external forces, is ultimately a disease primarily driven by aberrations observed in the molecular genetics of the tumor. Research studying PCa predominantly from European American men shows that indolent and advanced or metastatic prostate tumors have distinguishing molecular genomic make-ups. Early yet increasing evidence suggests that clinically distinct PCa from AAM also display molecular distinctions. It is reasonable to predict that further study will reveal molecular subtypes and various frequencies for PCa subtypes among diverse patient groups, thereby providing insight as to the genomic lesions and gene signatures that are functionally implicated in carcinogenesis or aggressive PCa in AAM. That knowledge will prove useful in developing strategies to predict who will develop advanced PCa among AAM and will provide the rationale to develop effective individualized treatment strategies to overcome disparities.
| S-EPMC5415277 | biostudies-literature
Project description:Prostate cancer prevalence in African Americans (AA) is over 1.5 times the prevalence in European Americans (EA). Among over a hundred index risk SNPs for prostate cancer, only a few can be verified using the available AAs' data. Their relevance to the prevalence inequality and other racial disparities has not been fully determined. We investigated this issue by an integrative analysis of five public datasets. We categorized the datasets into two classes. The training class consisted of the datasets generated by three genome-wide association studies. The test class contained the prostate adenocarcinoma data of The Cancer Genome Atlas and the data of African and European super-populations in the 1000-Genome project. The polygenic risk scores (PRS) of test samples for cancer occurrence were calculated according to the effects of genetic variants estimated from the training samples. We obtained the following findings. Africans' PRSs are higher than Europeans' scores (P < 1 × 10-6). AA patients' PRSs are higher than EA patients' scores (P < 3×10-9). The patients with tumors presenting fusion or abnormal expression in ERG and other E26 transformation-specific (ETS) family genes have lower PRSs than the patients without such aberrations (P < 7×10-5). Five tumor progression-related genes have the expression levels being significantly correlated with PRS (FDR < 0.01). Additional simulation analysis shows that the high prostate cancer prevalence in African populations makes it challenging to identify individual risk variants using African men's data. These results implicate that the index risk SNP-based PRS is compatible with the observed racial disparity in prostate cancer prevalence and ETS abnormal cancers may be less heritable compared with other subtypes.Prevention relevanceThis study reveals the relevance of index risk SNP markers with racial disparities in prostate cancer. The findings also indicate that PRS can be used in prostate cancer subtype prediction.
| S-EPMC8929532 | biostudies-literature
Project description:BackgroundRacial disparities in cancer outcomes are increasingly recognized, but comprehensive analyses, including molecular studies, are limited. The objective of the current study was to perform a pan-cancer clinical and epigenetic molecular analysis of outcomes in African American (AA) and European American (EA) patients.MethodsCross-platform analyses using cancer databases (the Surveillance, Epidemiology, and End Results program database and the National Cancer Data Base) and a molecular database (The Cancer Genome Ancestry Atlas) were performed to evaluate clinical and epigenetic molecular differences between AA and EA patients based on genetic ancestry.ResultsIn the primary pan-cancer survival analysis using the Surveillance, Epidemiology, and End Results database (2,045,839 patients; 87.5% EA and 12.5% AA), AA patients had higher mortality rates for 28 of 42 cancer types analyzed (hazard ratio, >1.0). AAs continued to have higher mortality in 13 cancer types after adjustment for socioeconomic variables using the National Cancer Database (5,150,023 patients; 11.6% AA and 88.4% EA). Then, molecular features of 5,283 tumors were analyzed in patients who had genetic ancestry data available (87.2% EA and 12.8% AA). Genes were identified with altered DNA methylation along with increased microRNA expression levels unique to AA patients that are associated with cancer drug resistance. Increased miRNAs (miR-15a, miR-17, miR-130-3p, miR-181a) were noted in common among AAs with breast, kidney, thyroid, or prostate carcinomas.ConclusionsThe current results identified epigenetic features in AA patients who have cancer that may contribute to higher mortality rates compared with EA patients who have cancer. Therefore, a focus on molecular signatures unique to AAs may identify actionable molecular abnormalities.
| S-EPMC6992510 | biostudies-literature
Project description:Prostate cancer mortality rates have decreased over recent decades, but racial disparities in prostate cancer survival still present as a serious challenge. These disparities may be impacted by age; in fact, African-American men younger than age 65 have prostate cancer mortality rates nearly three times greater than that of White men. Therefore, a systematic literature review was conducted in Medline and EMBASE databases focusing on articles comparing survival and mortality rates for prostate cancer patients across age and race.Articles included were based on the following criteria: (1) included African-American and White prostate cancer patients residing in the US; (2) measured racial disparities across distinct age categories with at least one category below and one above age 65; and (3) addressed racial disparities in terms of overall survival or mortality.Twenty eight articles compared survival and mortality disparities between African-American and White prostate cancer patients across different age categories. Of the 28 articles, 19 articles (68%) showed disparities decreased with age, 8 articles (29%) showed disparities constant with age, and 1 article (3%) showed disparities increased with age.More often the survival and mortality gap between African-American and White prostate cancer patients decreases with age. Additional studies are needed to elucidate other factors that may influence racial disparities in prostate cancer patients. These results provide insight into the racial disparities in prostate cancer and suggest more resources should be directed towards decreasing the disparity gap in younger prostate cancer patients.
| S-EPMC5573592 | biostudies-literature
Project description:Black men are disproportionately affected by prostate cancer (PCa), with earlier presentation, more aggressive disease, and higher mortality rates versus White men. Furthermore, Black men have less access to PCa treatment and experience longer delays between diagnosis and treatment. In this review, the authors discuss the factors contributing to racial disparities and present solutions to improve access to care and increase clinical trial participation among Black men with PCa. Racial disparities observed among Black men with PCa are multifaceted, evolving from institutional racism. Cultural factors include generalized mistrust of the health care system, poor physician-patient communication, lack of information on PCa and treatment options, fear of PCa diagnosis, and perceived societal stigma of the disease. In the United States, geographic trends in racial disparities have been observed. Economic factors, e.g., cost of care, recovery time, and cancer debt, play an important role in racial disparities observed in PCa treatment and outcomes. Racial diversity is often lacking in genomic and precision medicine studies. Black men are largely underrepresented in key phase 3 PCa trials and may be less willing to enroll in clinical trials due to lack of awareness, lack of diversity in clinical trial research teams, and bias of health care providers to recommend clinical research. The authors propose solutions to address these factors that include educating clinicians and institutions on the barriers Black men experience, increasing the diversity of health care providers and clinical research teams, and empowering Black men to be involved in their treatment, which are keys to creating equity for Black men with PCa. LAY SUMMARY: Prostate cancer negatively affects Black men more than men of other races. The history of segregation and mistreatment in the health care system may contribute to mistrust among Black men. Outcomes are worse for Black men because they are less likely to be screened or to receive treatment for prostate cancer. Black men also are unlikely to participate in clinical research, making it difficult for investigators to understand how Black men are affected by prostate cancer. Suggestions for addressing these differences include teaching physicians and nurses about the issues Black men experience getting treatment and improving how Black men get information on prostate cancer.
| S-EPMC9826514 | biostudies-literature
Project description:In the United States, African American (AA) men have a 2.4 times higher mortality rate due to prostate cancer than White men. The multifactorial causes of the racial disparities in prostate cancer involve various social determinants of health, socioeconomic status, and access to healthcare. However, emerging evidence also suggests that circadian rhythm disruption (CRD) contributes to prostate cancer, and AA men may be more susceptible to developing CRDs. Circadian rhythms play a significant role in metabolism, hormone secretion, and sleep/wake cycles. Disruption in these circadian rhythms can be caused by airplane travel/jetlag, night shift work, exposure to light, and neighborhood noise levels, which can contribute to sleep disorders and chronic conditions such as obesity, diabetes, cardiovascular disease, and depression. The drivers of the racial disparities in CRD include night shift work, racial discrimination, elevated stress, and residing in poor neighborhoods characterized by high noise pollution. Given the increased vulnerability of AA men to CRDs, and the role that CRDs play in prostate cancer, elucidating the clock-related prostate cancer pathways and their behavior and environmental covariates may be critical to better understanding and reducing the racial disparities in prostate cancer.
| S-EPMC9600368 | biostudies-literature
Project description:ObjectiveTo conduct a prospective study to examine whether there are pretreatment and post-treatment disparities in urinary, sexual, and bowel quality of life (QOL) by race or ethnicity, education, or income in men with clinically localized prostate cancer (PCa.) METHODS: Participants (N = 1508; 81% white; 12% black; 7% Hispanic; 50% surgery; 27% radiotherapy; 23% active surveillance) completed the Expanded Prostate Cancer Index Composite measure of PCa-specific QOL prior to treatment, 6 weeks, 6, 12, 18, and 24 months after treatment. We analyzed pretreatment differences in QOL with multivariable linear regression and post-treatment differences with generalized estimating equation models.ResultsBlacks and Hispanics (compared with whites) and men with lower income had worse pretreatment urinary function; poorer and less educated men had worse pretreatment sexual function (P < .05). In adjusted models, among men treated surgically, blacks and Hispanics had worse bowel function compared with whites, and men with lower income experienced more sexual bother and slower recovery in urinary function. Not all racial or ethnic differences favored whites; blacks had higher sexual function than whites prior to surgery and improved faster after surgery. Blacks receiving radiotherapy had lower post-treatment bowel bother than whites (P < .05).ConclusionControlling for baseline QOL, there were some post-treatment disparities in urinary and sexual QOL that suggest the need to investigate whether treatment quality and access to follow-up care is equitable. However, survivorship disparities may, to a greater extent, reflect disadvantages in baseline health that exacerbate QOL issues after treatment.
| S-EPMC5826752 | biostudies-literature
Project description:BACKGROUND:Racial disparities in prostate cancer survival (PCS) narrowed during the prostate-specific antigen (PSA) era, suggesting that screening may induce more equitable outcomes. However, the effects of lead time and overdiagnosis can inflate survival even without real screening benefit. METHODS:A simulation model of PCS in the early PSA era (1991-2000) was created. The modeled survival started with baseline survival in the pre-PSA era (1975-1990) and added lead times and overdiagnosis using estimates from published studies. The authors quantified 1) discrepancies between modeled and observed PCS in the PSA era and 2) residual period effects on PCS given specified values for screening benefit. RESULTS:Lead time and overdiagnosis explained more of the improvement in PCS for older ages at diagnosis (46% [95% confidence interval (CI), 44%-50%] for blacks and 51% [95% CI, 50%-52%] for all races ages 50-54 years vs 98% [95% CI, 97%-99%] for blacks and 100% for all races ages 75-79 years). They also explained more of the narrowing in PCS disparities for older ages (33% [95% CI, 31%-43%] for men ages 50-54 years vs 74% [95% CI, 71%-81%] for men ages 75-79 years). The period effects amounted to reductions of 27% to 40% among blacks and 26% to 38% among all races in the risk of prostate cancer death, depending on the screening benefit. CONCLUSIONS:Real improvements in survival disparities in the PSA era are smaller than those observed and reflect similar reductions in the risk of prostate cancer death among blacks and all races. Understanding screening artifacts is necessary for valid interpretation of observed survival trends. Cancer 2018;124:1752-9. © 2018 American Cancer Society.
| S-EPMC5891383 | biostudies-literature
Project description:Individuals of African descent are disproportionately affected by specific complex diseases, such as breast and prostate cancer, which are driven by both biological and nonbiological factors. In the case of breast cancer, there is clear evidence that psychosocial factors (environment, socioeconomic status, health behaviors, etc.) have a strong influence on racial disparities. However, even after controlling for these factors, overall phenotypic differences in breast cancer pathology remain among groups of individuals who vary by geographic ancestry. There is a growing appreciation that chronic/reoccurring inflammation, primarily driven by mechanisms of innate immunity, contributes to core functions associated with cancer progression. Germline mutations in innate immune genes that have been retained in the human genome offer enhanced protection against environmental pathogens, and protective innate immune variants against specific pathogens are enriched among populations whose ancestors were heavily exposed to those pathogens. Consequently, it is predicted that racial/ethnic differences in innate immune programs will translate into ethnic differences in both pro- and antitumor immunity, tumor progression, and prognosis, leading to the current phenomenon of racial/ethnic disparities in cancer. This review explores examples of protective innate immune genetic variants that are (i) distributed disproportionately among racial populations and (ii) associated with racial/ethnic disparities of breast and prostate cancer.
| S-EPMC6730653 | biostudies-literature