Dataset Information

Genomic differences between black and white patients implicate a distinct immune response to papillary renal cell carcinoma.

ABSTRACT: Significant disparities in survival, incidence and possibly response to current therapies exist between black and white patients with renal cell carcinoma (RCC). Recent genomic evidence to account for these disparities has been reported for clear cell RCC. However, racial disparities at the genomic level for papillary RCC (pRCC) which is a genetically distinct and less responsive histologic subtype of RCC have not been reported. Using The Cancer Genome Atlas (TCGA) data, the present study assessed gene-level expression, somatic mutation and pathway differences between 58 black and 58 white patients with pRCC propensity matched on age, gender and pathologic T stage. Distinct tumor biology with differential expression patterns were observed in black vs. white patients with pRCC. Specifically, significance analysis of microarrays was applied to TCGA gene expression data and identified 163 genes and 120 genes overexpressed in black and white patients, respectively (FDR q<0.05). Gene Set Enrichment Analysis identified 62 gene sets enriched (p<0.10) in blacks. Enrichment of immune immune system pathways were noted in black patients. These included the B cell receptor signaling pathway, the NOD-like receptor signaling pathway and genes involved in defensins. The VEGF pathway was also more significant in black patients. CRYBB2, a gene associated with the WNT pathway was overexpressed in Black patients. While our data requires validation, these findings suggest that race may have implications for distinct immune responses to cancer and that the use of immunotherapies, and VEGFR inhibitors to target these pathways may improve survival in black patients with advanced pRCC.

SUBMITTER: Paulucci DJ

PROVIDER: S-EPMC5354901 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic differences between black and white patients implicate a distinct immune response to papillary renal cell carcinoma.

Paulucci David J DJ Sfakianos John P JP Skanderup Anders J AJ Kan Kathleen K Tsao Che-Kai CK Galsky Matthew D MD Hakimi A Ari AA Badani Ketan K KK

Oncotarget 20170101 3

Significant disparities in survival, incidence and possibly response to current therapies exist between black and white patients with renal cell carcinoma (RCC). Recent genomic evidence to account for these disparities has been reported for clear cell RCC. However, racial disparities at the genomic level for papillary RCC (pRCC) which is a genetically distinct and less responsive histologic subtype of RCC have not been reported. Using The Cancer Genome Atlas (TCGA) data, the present study assess ...[more]

PMID: 28029648

Similar Datasets

Project description:ImportanceThere 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.ObjectiveTo determine if there are racial differences in the somatic mutation rate and gene expression of ccRCC tumors from white and African American patients.Design, setting, and participantsOverall, 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.Main outcomes and measuresThe comparison of somatic mutation rates and differences in RNA expression in white and African American patients with ccRCC.ResultsOverall, 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.Conclusions and relevanceAfrican 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.

Project description:BackgroundRenal cell carcinoma and hypertension (a well-established renal cancer risk factor) are both more frequent among blacks than whites in the United States. The association between hypertension and renal cell carcinoma has not been examined in black Americans. We investigated the hypertension-renal cancer association by race, and we assessed the role of hypertension in the racial disparity of renal cancer incidence.MethodsParticipants were enrolled in a population-based case-control study in Detroit and Chicago during 2002-2007 (number of cases: 843 whites, 358 blacks; number of controls: 707 whites, 519 blacks). Participants reported their history of hypertension and antihypertensive drug use. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for demographic characteristics, smoking, body mass index, and family history of cancer.ResultsHypertension doubled renal cancer risk (OR = 2.0 [CI = 1.7-2.5]) overall. For whites, the OR was 1.9 (CI = 1.5-2.4), whereas for blacks it was 2.8 (2.1-3.8) (P for interaction = 0.11). ORs increased with time after hypertension diagnosis (P for trend <0.001), reaching 4.1 (CI = 2.3-7.4) for blacks and 2.6 (CI = 1.7-4.1) for whites after 25 years. ORs for poorly controlled hypertension were 4.5 (CI = 2.3-8.8) for blacks and 2.1 (CI = 1.2-3.8) for whites. If these estimates correctly represent causal effects and if, hypothetically, hypertension could be prevented entirely among persons aged 50-79 years, the black/white disparity in renal cancer could be reversed among women and reduced by two-thirds among men.ConclusionsHypertension is a risk factor for renal cancer among both blacks and whites, and might explain a substantial portion of the racial disparity in renal cancer incidence. Preventing and controlling hypertension might reduce renal cancer incidence, adding to the known benefits of blood pressure control for heart disease and stroke reduction, particularly among blacks.

Dataset Information

Genomic differences between black and white patients implicate a distinct immune response to papillary renal cell carcinoma.

Publications

Genomic differences between black and white patients implicate a distinct immune response to papillary renal cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets