Dataset Information

Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence.

ABSTRACT:

Purpose

African American women are more likely to die as a result of breast cancer than white women. The influence of somatic genomic profiles on this racial disparity is unclear. We aimed to compare the racial distribution of tumor genomic characteristics and breast cancer recurrence.

Methods

We assessed white and African American women with stage I to III breast cancer diagnosed from 1988 to 2013 and primary tumors submitted to The Cancer Genome Atlas from 2010 to 2014. We used Cox proportional hazards models to evaluate the association of race and genetic traits with tumor recurrence.

Results

We investigated exome sequencing and gene expression data in 663 and 711 white and 105 and 159 African American women, respectively. African Americans had more TP53 mutations (42.9% v 27.6%; P = .003) and fewer PIK3CA mutations (20.0% v 33.9%; P = .008). Intratumor genetic heterogeneity was greater in African American than white tumors overall by 5.1 units (95% CI, 2.4 to 7.7) and within triple-negative tumors by 4.1 units (95% CI, 1.4 to 6.8). African Americans had more basal tumors by the 50-gene set predictor using the predication analysis of microarray method (PAM50; 39.0% v 18.6%; P < .001) and fewer PAM50 luminal A tumors (17.0% v 34.7%; P < .001). Among triple-negative subtypes, African Americans had more basal-like 1 and mesenchymal stem-like tumors. African Americans had a higher risk of tumor recurrence than whites (hazard ratio, 2.22; 95% CI, 1.05 to 4.67). Racial differences in TP53 mutation, PAM50 basal subtype, and triple-negative tumor prevalence but not intratumor genetic heterogeneity influenced the magnitude and significance of the racial disparity in tumor recurrence.

Conclusion

African Americans had greater intratumor genetic heterogeneity and more basal gene expression tumors, even within triple-negative breast cancer. This pattern suggests more aggressive tumor biology in African Americans than whites, which could contribute to racial disparity in breast cancer outcome.

SUBMITTER: Keenan T

PROVIDER: S-EPMC4979243 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Publications

Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence.

Keenan Tanya T Moy Beverly B Mroz Edmund A EA Ross Kenneth K Niemierko Andrzej A Rocco James W JW Isakoff Steven S Ellisen Leif W LW Bardia Aditya A

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20150914 31

<h4>Purpose</h4>African American women are more likely to die as a result of breast cancer than white women. The influence of somatic genomic profiles on this racial disparity is unclear. We aimed to compare the racial distribution of tumor genomic characteristics and breast cancer recurrence.<h4>Methods</h4>We assessed white and African American women with stage I to III breast cancer diagnosed from 1988 to 2013 and primary tumors submitted to The Cancer Genome Atlas from 2010 to 2014. We used ...[more]

PMID: 26371147

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Project description:Importance: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. Objective:To 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 Participants: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. Main Outcomes and Measures:The comparison of somatic mutation rates and differences in RNA expression in white and African American patients with ccRCC. Results: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. Conclusions and Relevance: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.

Dataset Information

Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence.

Purpose

Methods

Results

Conclusion

Publications

Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence.

Similar Datasets

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