Survival Of White Patients Research Articles

Abstract 6535: Identification of coding and non-coding genes associated with survival outcomes in uterine cancer

Abstract Endometrial (or uterine) cancer is the most commonly diagnosed cancer in the female reproductive system and it disproportionately affects Black women, who are twice as likely to die from the disease than White women. In this study, we focused on the molecular characterization of copy-number high (CN-high) molecular subclassification of uterine cancer tumors, which includes most serous and serous-like endometroid tumors. These poorly characterized subcategories account for less than 10% of all uterine cancers but are responsible for over 80% of the mortality in uterine cancers and occur more commonly in Black women.We leveraged publicly available Pan-Cancer Atlas data to perform differential gene expression analyses between control and cancer samples in the Black and White CN-high groups with the aim of identifying relevant genes that could play a role in the aggressiveness of this cancer. We then performed survival analysis using the genes of interest using Kaplan-Meier estimators to ascertain the gene-specific survival outcomes.In the significantly upregulated subset of genes, we found that the high expression of the candidate gene was associated with higher survival in both White patients (p=0.046), and Black patients (p=0.021). Additionally, the expression levels of one of the noncoding genes were associated with differential survival between the groups, with low expression being associated with higher survival in White patients (p=0.0045), and high expression associated with higher survival in Black patients (p=0.018). This differential association of survival was also observed in one of the most downregulated genes in both groups, with low expression predicting higher survival in white patients (p=0.004), and Black patient survival is associated with high expression (p=0.0082). We also identified novel non-coding genes that predicted different survival outcomes in both groups, with high expression predicting better survival in Black patients and low expression predicting better survival in White patients (p=0.048 and p=0.039, respectively). These results showcase the identification of both coding and noncoding potential genomic targets that are associated with clinical outcomes in the aggressive CN-high molecular subtype of uterine cancer. These targets merit further characterization and experimental validation to elucidate their molecular roles in the progression of endometrial cancer. Acknowledgments S.S.G. is a CPRIT scholar in cancer research and is supported by a First-time Faculty Recruitment Award from the Cancer Prevention and Research Institute of Texas (CPRIT; RR170020). S.S.G. is also supported by a) the Lizanell and Colbert Coldwell Foundation, b) The Edward N. and Margaret G. Marsh Foundation, and c) the American Cancer Society. Citation Format: Enrique I. Ramos, Axel M. Hidalgo, Ken Y. Lin, Shrikanth S. Gadad. Identification of coding and non-coding genes associated with survival outcomes in uterine cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6535.

Abstract PO-172: Impact of African ancestry on the relationship between body mass index (BMI) and survival in early stage breast cancer: Retrospective analysis from E5103

Abstract Purpose: Both African American (AA) race and obesity are associated with worse survival in early stage breast cancer. Obesity disproportionately affects AA women, and may further racial disparities in breast cancer. Prior work investigating the intersection of race, BMI, and outcome in the large adjuvant trial E1199 found obesity to be prognostic of worse survival in White patients, with no significant impact on the disparately inferior survival outcomes seen in Black patients. However, this analysis was based on self-reported race, which neglects underlying genetic ancestry that may drive biologic differences. Here, we investigate the impact of BMI on outcomes in patients of African or European ancestry in the phase III adjuvant breast cancer trial E5103. Methods: E5103 enrolled patients with high risk, HER2 negative, early stage breast cancer to receive adjuvant doxorubicin and cyclophosphamide for 4 cycles, followed by 12 weeks of weekly paclitaxel, with or without bevacizumab. Genetic ancestry was determined on the 3,373 patients with available germline DNA, BMI, and outcome data using principal components from a genome-wide array. The primary objective was to assess the impact of BMI on disease free survival (DFS) and overall survival (OS) by ancestry. A univariate Cox proportional hazard model was used to evaluate the correlation between continuous or binary BMI and survival in AA or European Americans (EA). Results: 11.6% (n=390) of patients were genetically classified as AA and 74.6% (n=2517) as EA. Higher BMI (increment of every 5 kg/m2) was significantly associated with worse DFS (HR=1.24, p=0.006) and OS (HR=1.38, p=0.005) only in AAs, but not in EAs (DFS p=0.76, OS p=0.35). Exploring BMI categories in AAs, survival differences were most significant between patients who had morbid obesity (BMI ≥40) and those who did not (DFS HR= 2.01, p=0.009; OS HR=2.19, p=0.045). However, in EAs, even morbid obesity was not associated with survival (DFS p=0.89, OS p=0.31). In the ER+ sub-population, BMI was associated with both DFS (HR=1.29, p=0.032) and OS (HR=1.60, p=0.017) in AAs, but only with OS in EAs (HR=1.15, p=0.049). In the triple negative sub-population, there was a trend toward worse survival with increasing BMI in AAs (p=0.098), but not in EAs (p=0.62). Conclusion: In contrast to prior work based on self-reported race, we found BMI to be significantly associated with worse survival in women of African ancestry in E5103, a large adjuvant trial that reflects our current approach to curative systemic therapy in breast cancer. Categorically, this association was significant only for morbid obesity, suggesting the relationship between BMI, race, and outcome may depend on the degree of obesity. Genetic ancestry may explain biologic differences driving both higher BMI and worse outcomes resulting in racial disparities in breast cancer. Citation Format: Tarah J. Ballinger, Guanglong Jiang, Fei Shen, Kathy D. Miller, Bryan P. Schneider. Impact of African ancestry on the relationship between body mass index (BMI) and survival in early stage breast cancer: Retrospective analysis from E5103 [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-172.

Abstract A110: Racial disparities in transitional cell carcinoma of the bladder: A population-based study

Abstract Introduction: Bladder cancer is among the most common cancers in the U.S. with an estimated 81,190 new cases diagnosed in 2018 as well as 17,240 estimated deaths. The vast majority, around 90%, of bladder cancer cases are transitional cell carcinoma. Due to the significant burden of the disease, and disparities in access to medical care, we aim to study the survival of patients diagnosed with transitional cell carcinoma based on ethnicity. Methods: Data of White and Black patients with transitional cell carcinoma of the bladder diagnosed between 1973 and 2014 were obtained using the SEER database. We compared the overall and cancer-specific survival of patients using Kaplan-Meier test and Cox models. Results: We reviewed a total of 199,535 patients with transitional cell carcinoma of the bladder, of whom 10,263 were blacks, while the others were whites. The median overall survival of white patients was 103 months (95%CI, 102.0.34-103.966), which was significantly better than the overall survival of black patients, which was 64 months (95%CI, 60.373-67.627). Bladder cancer-specific survival was also better for whites when compared to blacks. When we adjusted age, sex, grade and stage of cancer, and undergoing surgery for bladder cancer, being black was associated with worse overall survival outcomes and cancer-specific survival outcomes (HR=1.263, 95%CI [1.227-1.300], P<.001) and (HR=1.396, 95%CI [1.342-1.451] P<.001), respectively. Conclusions: Our results show that significant differences in cancer-specific survival between ethnicities with the majority of diagnosed patients being Whites, while Blacks are suffering from worse survival outcomes. More research can shine a light on the underlying reasons why ethnicity is a significant factor affecting the survival of patients with bladder cancer. Citation Format: Mohamed M. Gad, Anas M. Saad, Mariam A. Obaid, Muneer J. Husseini. Racial disparities in transitional cell carcinoma of the bladder: A population-based study [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A110.

Racial disparity of stage III rectal cancer among young adults: A combined NCDB/SEER analysis.

85 Background: With the advent of screening colonoscopy in 1997, there has been an overall decreasing incidence in rectal cancer. Recently, the ACS updated guidelines to started screening patients at 45 years old. The purpose of this study was to further investigate incidence and overall survival trends for rectal cancer among young white and African-American (AA) patients using the SEER and NCDB databases. Methods: Rectal cancer incidence trends in SEER-9/SEER-18 were analyzed for patients < 50 years old. Treatment and survival outcomes were also evaluated using the NCDB (2004-2014). White and AA patients were matched using propensity score analysis and inverse probability of treatment weighting (IPTW). Baseline characteristics were compared with Pearson Chi Square, before and after matching. Univariate and multivariable analyses were performed with Kaplan-Meier and Cox proportional hazard modeling, incorporating the IPTW-adjusted population. Results: 6,144 (SEER) and 17,819 (NCDB) young, white or AA patients were identified. There was an overall increase in incidence of stage III (APC 5.57, P < 0.05) and IV (APC 4.66, P < 0.05) rectal cancer among young white patients. For the entire population, there was improved overall survival for white patients compared to AA patients, even after adjusting for confounding factors. Subset analysis of both the SEER and NCDB databases revealed that the largest disparity was between AAn and white rectal cancer patients, is among the Stage III subset with HR of 1.6 (P < 0.001) and HR of 1.4 (P < 0.001), respectively. Conclusions: There is an alarming increase in younger patients being diagnosed with rectal cancer. Specifically, there appears to be more locally advanced rectal cancer among younger patients and a racial disparity favoring whites for survival outcomes was identified. This research further supports the utility of earlier screening and to identify the factors involved in this rise in rectal cancer incidence.

Mo1421 - Male Sex is a Risk Factor for Poorer Long-Term Overall Survival for White Patients with Hepatocellular Carcinoma (HCC) but not for Black Patients with HCC

Mo1421 - Male Sex is a Risk Factor for Poorer Long-Term Overall Survival for White Patients with Hepatocellular Carcinoma (HCC) but not for Black Patients with HCC

Disparity in survival between White and Asian patients with uterine serous carcinoma: Changes in clinical characteristics, pattern of care, and outcome over time from 1988 to 2011

Objectives: Our study uses the Surveillance, Epidemiology, and End Result (SEER) database to determine if outcome disparities between white and Asian patients with uterine serous carcinoma (USC) have changed over time. Methods: Women with USC were identified using the SEER database from 1988 to 2011 (n = 8,230), and grouped into 2 cohorts: white and Asian patients. Years of the study were divided into 3 periods (1988–1997, 1998–2004, and 2005–2011). Overall survival (OS) was estimated. Kaplan-Meier survival curves and Cox regression models were used. Results: Asians were younger but no difference was noted in stage distribution, marital status, cancer-directed surgery, extent of lymphadenectomy, and radiation therapy over the 2 time periods compared with whites. In multivariable analysis, after adjusting for age, race, marital status, stage, cancer-directed surgery, extent of lymphadenectomy, adjuvant radiation, and geographic location, Asian patients were 29% less likely to die than were whites (HR 0.71, 95% CI 0.53–0.96, P = .023) in the period 1988–1997. However, this difference disappeared in the periods 1999 to 2004 (HR 1.13, 95% CI 0.89–1.44, P = .30) and 2005 to 2011 (HR 1.1, 95% CI 0.86–1.34, P = .55). In multivariable analysis, the survival for white patients with USC significantly improved over the 3 time periods (P = .004 and <.0002 for 1998–2004 and 2005–2011, respectively). On the other hand, no difference in outcome was seen in Asian patients with USC during the 3 periods (P = .09 and P = .32 for 1998–2004 and 2005–2011, respectively). Conclusions: The survival difference between Asian and white patients with USC disappeared over time. White but not Asian patients with USC had improved outcome over time.

Intrinsic Genomic Differences Between African American and White Patients With Clear Cell Renal Cell Carcinoma.

There are well-documented racial disparities in outcomes for African American patients with clear cell renal cell carcinoma (ccRCC). Despite a dramatic improvement in overall survival in white patients since the advent of targeted therapy, survival for African Americans with advanced ccRCC has not changed. There is little known about potential racial differences in tumor biology of ccRCC. To determine if there are racial differences in the somatic mutation rate and gene expression of ccRCC tumors from white and African American patients. Overall, 438 patients with ccRCC were identified through The Cancer Genome Atlas (TCGA) clear cell kidney (KIRC) dataset (419 white and 19 African American patients). The GSE25540 dataset containing 135 patients (125 white and 10 African American patients) was used for validation. Tumor samples were collected from numerous cancer centers and were examined for racial differences in somatic mutation rates and RNA expression. Racial differences in somatic mutation rates and RNA expression were examined. The comparison of somatic mutation rates and differences in RNA expression in white and African American patients with ccRCC. Overall, 419 ccRCC tumor data sets from non-Hispanic white patients and 19 from non-Hispanic African American patients were identified through the publically available TCGA KIRC data set, and a validation set of 125 white and 10 African American ccRCC patient tumors was identified from the publicly available GSE25540 data set. African American patients were significantly less likely than white patients to have VHL mutations (2 of 12 [17%] vs 175 of 351 [50%], respectively; P = .04) and were enriched in the ccB molecular subtype (79% in African American vs 45% in white patients ; P = .005), a molecular subtype that carries a worse prognosis. It was found that RNA expression analysis revealed relative down-regulation of hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF)-associated pathways in African American patients compared with white patients. African American patients have less frequent VHL inactivation, are enriched in the ccB molecular subtype, and have decreased up-regulation of HIF-associated gene signatures than white patients. These genomic differences would predict decreased responsiveness to VEGF-targeted therapy and are a biologically plausible contributing factor to the worse survival of African American patients with ccRCC, even in the targeted therapy era.

Analysis of racial disparities in stage IIIC epithelial ovarian cancer care and outcomes in a Tertiary Gynecologic Oncology Referral Center

Objective To examine disparities in delivery of care and survival according to racial classification among White and African-American women with Stage IIIC epithelial ovarian cancer undergoing initial treatment in a tertiary referral center setting. Methods All consecutive patients diagnosed with Stage IIIC epithelial ovarian cancer between 1/1/95 and 12/31/08 were identified and clinic-pathologic variables retrospectively collected. Differences in initial treatment paradigm, surgical and adjuvant therapy, and overall survival according to racial classification were assessed by univariate and multivariate analyses. Results A total of 405 patients (White, n = 366; African-American, n = 39) were identified. There were no significant differences according to racial classification in age, CA125, ASA class, histology, tumor grade, the frequency of initial surgery (90.4% vs 82.1%, p = 0.06), optimal residual disease (73.0% vs 69.2%, p = 0.28), no gross residual disease (51.4% vs 53.8%, p = 0.49), and platinum-taxane chemotherapy (88.3% vs 87.2%, p = 0.55). The median overall survival for White patients was 50.5 months (95%CI = 43.2–57.9 months), compared to 47.0 (95%CI = 36.2–57.8) months for African-Americans ( p = 0.57). On multivariate analysis, age, tumor grade 3, serum albumin < 3.0 g/dl, platinum-based chemotherapy, and no gross residual disease were independently associated with overall survival, while African-American race was not (HR = 1.06, 95%CI = 0.61–1.79). Conclusions Among women undergoing initial treatment for ovarian cancer at a tertiary referral center, African-American patients were as likely as White patients to undergo cytoreductive surgery, be left with minimal post-surgical residual disease, and receive appropriate chemotherapy. With equal access to gynecologic oncology care and multidisciplinary cancer resources, the survival disparities according to race observed in population-based studies are largely mitigated.

Germline Polymorphisms in EGFR and Survival in Patients With Lung Cancer Receiving Gefitinib

The purpose of this study was to evaluate associations between germline epidermal growth factor receptor (EGFR) variants involved in transcriptional regulation and overall survival in white patients with non-small-cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor, gefitinib. Of 175 consecutive patients treated with oral gefitinib (250 mg/day), 170 (median age: 67 years; 72% men) were evaluable for genotyping and survival. Fifty-five patients (33%) had stable disease and 17 (10%) had an objective response. The most common of four haplotypes was G-C (EGFR*1) at the EGFR -216G>T and -191C>A loci (frequency, 0.45). After adjusting for performance status, previous platinum-containing chemotherapy and occurrence of skin rash or diarrhea during the first treatment cycle in patients with performance status 0 or 1 (N=139), the absence of EGFR*1 was associated with significantly better survival (hazard ratio: 0.54; 95% confidence interval: 0.32-0.91; P=0.015). The results may help identify patients with NSCLC who can benefit from gefitinib treatment.

Survival of patients undergoing renal replacement therapy in one center with special emphasis on racial differences

This study compared racial differences in end-stage renal disease (ESRD) in 550 patients starting renal replacement therapy at a large academic dialysis center between January 1, 1990, and December 31, 1993, with follow-up through December 31, 1994. Patient groups were compared with respect to cause of ESRD, comorbid factors at the start of dialysis therapy, choice of modality, transplantation rate, and survival. Fifty-eight percent of the patients were white and 42% were African-American. There was a similar distribution of causes of ESRD between races. African-American patients were less likely to choose peritoneal dialysis as initial therapy (11.6% v 29.3%; P < 0.001) and were less likely to change dialysis modality. Transplantation rates were significantly different between African-American and white patients (9.3% v 27.6%; P < 0.001). African-Americans less frequently received living-related, living-nonrelated, and cadaveric renal transplants. Given differences in transplantation rates and in survival of transplanted patients versus patients on dialysis, survival analysis was performed without censoring for transplantation. A multivariate Cox proportional hazards model was formed, and the following were identified as being significant independent predictors of survival: age, race, age-race interaction, serum albumin at the start of dialysis, activity level at the start of dialysis, and presence of congestive heart failure and cancer. Age had little effect on survival among African-American patients, while it was a significant predictor of survival in white patients. In the group of patients starting dialysis before the age of 30 years, African-American patients had a significantly increased mortality risk compared with white patients. However, white patients older than 50 years had a higher mortality risk; this risk difference increased with age. Racial differences in mortality among older white patients could not be explained by differences in comorbid conditions, transplantation rates, or withdrawal from dialysis.