Identification of Candidate Biomarker and Drug Targets for Improving Endometrial Cancer Racial Disparities.
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ABSTRACT:
SUBMITTER: Javadian P
PROVIDER: S-EPMC9318530 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionAlthough black patients with endometrial cancer (EC) have worse survival compared with white patients, the interaction between age/race has not been examined. The primary objective was to evaluate the impact of age at diagnosis on racial disparities in disease presentation and outcome in EC.MethodsWe evaluated women diagnosed with EC between 1991 and 2010 from the Surveillance, Epidemiology, and End Results. Mutation status for TP53 or PTEN, or with the aggressive integrative, transcript-based, or somatic copy number alteration-based molecular subtype were acquired from the Cancer Genome Atlas. Logistic regression model was used to estimate the interaction between age and race on histology. Cox regression model was used to estimate the interaction between age and race on survival.Results78,184 white and 8518 black patients with EC were analyzed. Median age at diagnosis was 3-years younger for black vs. white patients with serous cancer and carcinosarcoma (P<0.0001). The increased presentation of non-endometrioid histology with age was larger in black vs. white patients (P<0.0001). The racial disparity in survival and cancer-related mortality was more prevalent in black vs. white patients, and in younger vs. older patients (P<0.0001). Mutations in TP53, PTEN and the three aggressive molecular subtypes each varied by race, age and histology.ConclusionsAggressive histology and molecular features were more common in black patients and older age, with greater impact of age on poor tumor characteristics in black vs. white patients. Racial disparities in outcome were larger in younger patients. Intervention at early ages may mitigate racial disparities in EC.
| S-EPMC6863162 | biostudies-literature
Project description:ObjectiveTo evaluate the association of race-ethnicity and neighborhood socioeconomic status with adherence to National Comprehensive Cancer Network guidelines for endometrial carcinoma.MethodsData are from the SEER (Surveillance, Epidemiology, and End Results) cancer registry of women diagnosed with endometrial carcinoma for the years 2006-2015. The sample included 83,883 women after inclusion and exclusion criteria were applied. Descriptive statistics, bivariate analyses, univariate, and multivariate logistic regression models were performed to evaluate the association between race-ethnicity and neighborhood socioeconomic status with adherence to treatment guidelines.ResultsAfter controlling for demographic and clinical covariates, Black (odds ratio [OR] 0.89, P<.001), Latina (OR .92, P<.001), and American Indian or Alaska Native (OR 0.82, P=.034) women had lower odds of receiving adherent treatment and Asian (OR 1.14, P<.001) and Native Hawaiian or Pacific Islander (OR 1.19 P=.012) women had higher odds of receiving adherent treatment compared with White women. After controlling for covariates, there was a gradient by neighborhood socioeconomic status: women in the high-middle (OR 0.89, P<.001), middle (OR 0.84, P<.001), low-middle (OR 0.80, P<.001), and lowest (OR 0.73, P<.001) neighborhood socioeconomic status categories had lower odds of receiving adherent treatment than the those in the highest neighborhood socioeconomic status group.ConclusionsFindings from this study suggest there are racial-ethnic and neighborhood socioeconomic disparities in National Comprehensive Cancer Network treatment adherence for endometrial cancer. Standard treatment therapies should not differ based on sociodemographics. Interventions are needed to ensure that equitable cancer treatment practices are available for all individuals, regardless of racial-ethnic or socioeconomic background.
| S-EPMC10403994 | biostudies-literature
Project description:ObjectiveLittle is known about the influence of hospital procedural volume on racial disparities for uterine cancer. We examined whether the magnitude of the survival differential between black and white women varied based on hospital procedural volume for endometrial cancer.MethodsWe utilized the National Cancer Data Base to examine women with endometrial cancer from 1998 to 2012. Annualized hospital procedural volume was calculated and hospitals grouped into volume-based quartiles. Multivariable models were developed to examine differences in two and five-year survival between black and white women across the hospital volume categories. Patients were classified as early or advanced stage and as type I (low grade, endometrioid) or type II (high grade endometrioid, other histologies) cancers.ResultsWe identified 243,422 (75.0%) white and 27,764 (8.6%) black women treated at 1059 hospitals. Regardless of hospital volume, black women had decreased survival. For each tumor class, the absolute difference in adjusted two-year survival between black and white women decreased with increasing hospital volume. For example, for women with early-stage, type I tumors, the adjusted two-year survival differential between blacks and whites was -1.4% (95%CI, -2.4 to -0.5%) at low volume centers and decreased to -0.5% (95%CI, -0.9 to 0%) at high-volume hospitals (P<0.0001). For advanced stage, type I tumors, the adjusted survival differential decreased from -12.4% (95%CI, -24.0 to -0.9%) to 1.2% (95%CI, -2.9 to 5.3%) at high volume hospitals (P<0.0001).ConclusionBlack race is an independent predictor of mortality. The impact of race on mortality is mitigated, albeit not eliminated, by increasing hospital volume.
| S-EPMC5915905 | biostudies-literature
Project description:ObjectiveThe mortality rate for Black women with endometrial cancer (EC) is double that of White women, although the incidence rate is lower among Black women. Unequal access to care may contribute to this racial disparity. This study aimed to assess whether survival varied between non-Hispanic Black (NHB) and non-Hispanic White (NHW) women with EC in the Military Health System (MHS) which provides equal access care to its beneficiaries despite racial/ethnic background.MethodsThe study was conducted using data from the U.S. Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR). Study subjects included NHB and NHW women with histologically confirmed and surgically managed EC diagnosed between 1988 and 2013. The study outcome was all-cause death. Overall survival between NHB and NHW women was compared using multivariable Cox modeling.ResultsThe study included 144 NHB and 1439 NHW women with EC. Kaplan-Meier curves showed NHB women had worse survival than NHW women (log-rank P < 0.0001). The disparity in survival between NHB and NHW women persisted after adjusting for age, diagnosis period, tumor stage, tumor histology/grade, and adjuvant treatment (HR = 1.64, 95% CI = 1.19 to 2.27). Multivariable analyses stratified by tumor features or treatment showed that the racial disparity was confined to women with low-risk features (stage I/II disease or low-grade EC) or no adjuvant treatment.ConclusionThere were racial differences in overall survival between NHB and NHW women with EC in the MHS equal access healthcare system, suggesting that factors other than access to care may be related to this racial disparity.
| S-EPMC8562590 | biostudies-literature
Project description:Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. A well recognized disparity by race in both incidence and survival outcome exists for this cancer. Specifically Caucasians are about two times more likely to develop endometrial cancer than are African-Americans. However, African-American women are more likely to die from this disease than are Caucasians. The basis for this disparity remains unknown. Previous studies have identified differences in the types and frequencies of gene mutations among endometrial cancers from Caucasians and African-Americans suggesting that the tumors from these two groups might have differing underlying genetic defects. We performed a gene expression microarray study in an effort to identify differentially expressed transcripts between African-American and Caucasian women's endometrial cancers. Our gene expression screen identified a list of potential biomarkers that are differentially expressed between these two groups of cancers. Of these we identified a poorly characterized transcript with a region of homology to phospho serine phosphatase (PSPH) and designated phospho serine phosphatase like (PSPHL) as the most differentially over-expressed gene in cancers from African-Americans. We further clarified the nature of expressed transcripts. Northern blot analysis confirmed the message was limited to a transcript of under 1?kB. Sequence analysis of transcripts confirmed two alternate open reading frame (ORF) isoforms due to alternative splicing events. Splice specific primer sets confirmed both isoforms were differentially expressed in tissues from Caucasians and African-Americans. We further examined the expression in other tissues from women to include normal endometrium, normal and malignant ovary. In all cases PSPHL expression was more often present in tissues from African-Americans than Caucasians. Our data confirm the African-American based expression of the PSPHL transcript in endometrial cancer and also identify its expression in other tissues from African-Americans including ovary and ovarian cancer. PSPHL represents a candidate gene that might influence the observed racial disparity in endometrial and other cancers.
| S-EPMC3389395 | biostudies-literature
Project description:Race and ethnicity are associated with risk of venous thromboembolism in population-based studies. Blacks/African Americans have a higher incidence, whereas Asians/Pacific Islanders and Hispanics have a lower incidence of venous thromboembolism compared with non-Hispanic Whites. The impact of race/ethnicity on the incidence of cancer-associated thrombosis (CAT), a common complication in patients with malignancy, has not been well defined. Using the California Cancer Registry linked to the California Patient Discharge Dataset and Emergency Department Utilization database, we studied a large, diverse cohort of patients (n = 942 109) from 2005 to 2017 with the 13 most common, first primary malignancies to determine the association between race/ethnicity and incidence of incident and recurrent CAT. Multivariable Cox proportional hazards regression models were performed to determine the effect of race/ethnicity on the risk of overall CAT, specific CAT by location, and recurrent CAT. Blacks/African Americans had a higher incidence of CAT for all tumor types except myeloma, whereas Asians/Pacific Islanders had a consistently lower incidence of CAT compared with non-Hispanic Whites, after adjusting for potential confounders. The main driver for the racial/ethnic differences was incidence of pulmonary embolism. We speculate the association of race/ethnicity with incidence of CAT may be partially because of underlying thrombotic predisposition that varies by ancestry, but we also must consider the impact of social determinants of health on our results.
| S-EPMC9131919 | biostudies-literature
Project description:The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6−33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein−protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan−Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers.
| S-EPMC9692821 | biostudies-literature
Project description:To assess differences in the receipt of preventive health services by race/ethnicity among older women with endometrial cancer enrolled in Medicare, we conducted a retrospective population-based cohort study of women diagnosed with endometrial cancer from 2001 to 2011 in the Surveillance Epidemiology and End Results (SEER)-Medicare database. Women with stage I or II endometrial cancer of epithelial origin were included. The exposure was race/ethnicity (Non-Hispanic [NH] White, NH Black, Hispanic, and NH Asian/Pacific Islander [PI]). The services examined were receipt of influenza vaccination and screening tests for diabetes mellitus, hyperlipidemia, and breast cancer. We used multivariate logistic regression to estimate odds ratios with 95% confidence intervals (CI) adjusted for age, region, and year of diagnosis. A total of 13,054 women were included. In the 2 years after diagnosis, receipt of any influenza vaccine ranged from 45% among NH Black women to 67% among NH White women; receipt of a mammogram ranged from 65% among NH Black women to 74% among NH White women. Relative to NH White women, NH Black women had a lower likelihood of receiving both influenza vaccination (adjusted odds ratio [aOR] 0.40, 95% CI 0.33-0.44) and screening mammography (aOR 0.64, 95% CI 0.52-0.79). Hispanic women also were less likely to receive influenza vaccination than NH White women (aOR 0.61, 95% CI 0.51-0.72). There were no significant differences across racial groups for diabetes or cholesterol screening services. Among older women with early-stage endometrial cancer, racial disparities exist in the utilization of some preventive services.
| S-EPMC5603841 | biostudies-other
Project description:Disparities in cancer survival may be related to differences in stage. Segregation may be associated with disparities in stage, particularly for cancers for which screening promotes survival.The objective of the study was to examine whether segregation modifies racial/ethnic disparities in stage.The design of the study was analysis of Surveillance, Epidemiology, and End Results Medicare data for seniors with breast, colorectal, lung, and prostate cancer (n = 410,870).The outcome was early- versus late-stage diagnosis. Area of residence was categorized into 4 groups: low segregation/high income (potentially the most advantaged), high segregation/high income, low segregation/low income, and high segregation/low income (possibly the most disadvantaged). Blacks were less likely than whites to be diagnosed with early-stage breast, colorectal, or prostate cancer, regardless of area. For colorectal cancer, the black/white disparity was largest in low-segregation/low-income areas (black/white odds ratio [OR] of early stage 0.51) and smallest in the most segregated areas (ORs 0.71 and 0.74, P < .005). Differences in disparities in stage by area category were not apparent for breast, prostate, or lung cancer. Whereas there were few Hispanic-white differences in early-stage diagnosis, the Hispanic/white disparity in early-stage diagnosis of breast cancer was largest in low-segregation/low-income areas (Hispanic/white OR of early stage 0.54) and smallest in high-segregation/low-income areas (OR 0.96, P < .05 compared to low-segregation/low-income areas).Disparities in stages for cancers with an established screening test were smaller in more segregated areas.
| S-EPMC2324162 | biostudies-other
Project description: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 growth. Racial differences have also been found among variants of genes of the enzymes involved in androgen biosynthesis and metabolism. Growth factors and their receptors are a potential cause of the disparity in PCa. Recent molecular and biotechnological approaches in the field of proteomics and genomics will greatly aid the advancement of translational research on racial disparity in PCa, which may help, in finding new prognostic markers and novel therapeutic approaches for the treatment of PCa in AA.
| S-EPMC5550772 | biostudies-literature