Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry

Abstract Breast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences in mortality, they do not fully explain disparity among women of African a...

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Autores principales:	Jessica Roelands, Raghvendra Mall, Hossam Almeer, Remy Thomas, Mahmoud G. Mohamed, Shahinaz Bedri, Salha Bujassoum Al-Bader, Kulsoom Junejo, Elad Ziv, Rosalyn W. Sayaman, Peter J. K. Kuppen, Davide Bedognetti, Wouter Hendrickx, Julie Decock
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/b9ef27825e2f4d69a5e91d3295cb1212
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spelling	oai:doaj.org-article:b9ef27825e2f4d69a5e91d3295cb12122021-12-02T13:30:14ZAncestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry10.1038/s41523-021-00215-x2374-4677https://doaj.org/article/b9ef27825e2f4d69a5e91d3295cb12122021-02-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00215-xhttps://doaj.org/toc/2374-4677Abstract Breast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences in mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab ancestry (ArA) compared to women of European ancestry (EA). In this study, we sought to identify molecular differences that could provide insight into the biology of ancestry-associated disparities in clinical outcomes. We applied a unique approach that combines the use of curated survival data from The Cancer Genome Atlas (TCGA) Pan-Cancer clinical data resource, improved single-nucleotide polymorphism-based inferred ancestry assignment, and a novel breast cancer subtype classification to interrogate the TCGA and a local Arab breast cancer dataset. We observed an enrichment of BasalMyo tumors in AA patients (38 vs 16.5% in EA, p = 1.30E − 10), associated with a significant worse overall (hazard ratio (HR) = 2.39, p = 0.02) and disease-specific survival (HR = 2.57, p = 0.03). Gene set enrichment analysis of BasalMyo AA and EA samples revealed differences in the abundance of T-regulatory and T-helper type 2 cells, and enrichment of cancer-related pathways with prognostic implications (AA: PI3K-Akt-mTOR and ErbB signaling; EA: EGF, estrogen-dependent and DNA repair signaling). Strikingly, AMPK signaling was associated with opposing prognostic connotation (AA: 10-year HR = 2.79, EA: 10-year HR = 0.34). Analysis of ArA patients suggests enrichment of BasalMyo tumors with a trend for differential enrichment of T-regulatory cells and AMPK signaling. Together, our findings suggest that the disparity in the clinical outcome of AA breast cancer patients is likely related to differences in cancer-related and microenvironmental features.Jessica RoelandsRaghvendra MallHossam AlmeerRemy ThomasMahmoud G. MohamedShahinaz BedriSalha Bujassoum Al-BaderKulsoom JunejoElad ZivRosalyn W. SayamanPeter J. K. KuppenDavide BedognettiWouter HendrickxJulie DecockNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jessica Roelands Raghvendra Mall Hossam Almeer Remy Thomas Mahmoud G. Mohamed Shahinaz Bedri Salha Bujassoum Al-Bader Kulsoom Junejo Elad Ziv Rosalyn W. Sayaman Peter J. K. Kuppen Davide Bedognetti Wouter Hendrickx Julie Decock Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry
description	Abstract Breast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences in mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab ancestry (ArA) compared to women of European ancestry (EA). In this study, we sought to identify molecular differences that could provide insight into the biology of ancestry-associated disparities in clinical outcomes. We applied a unique approach that combines the use of curated survival data from The Cancer Genome Atlas (TCGA) Pan-Cancer clinical data resource, improved single-nucleotide polymorphism-based inferred ancestry assignment, and a novel breast cancer subtype classification to interrogate the TCGA and a local Arab breast cancer dataset. We observed an enrichment of BasalMyo tumors in AA patients (38 vs 16.5% in EA, p = 1.30E − 10), associated with a significant worse overall (hazard ratio (HR) = 2.39, p = 0.02) and disease-specific survival (HR = 2.57, p = 0.03). Gene set enrichment analysis of BasalMyo AA and EA samples revealed differences in the abundance of T-regulatory and T-helper type 2 cells, and enrichment of cancer-related pathways with prognostic implications (AA: PI3K-Akt-mTOR and ErbB signaling; EA: EGF, estrogen-dependent and DNA repair signaling). Strikingly, AMPK signaling was associated with opposing prognostic connotation (AA: 10-year HR = 2.79, EA: 10-year HR = 0.34). Analysis of ArA patients suggests enrichment of BasalMyo tumors with a trend for differential enrichment of T-regulatory cells and AMPK signaling. Together, our findings suggest that the disparity in the clinical outcome of AA breast cancer patients is likely related to differences in cancer-related and microenvironmental features.
format	article
author	Jessica Roelands Raghvendra Mall Hossam Almeer Remy Thomas Mahmoud G. Mohamed Shahinaz Bedri Salha Bujassoum Al-Bader Kulsoom Junejo Elad Ziv Rosalyn W. Sayaman Peter J. K. Kuppen Davide Bedognetti Wouter Hendrickx Julie Decock
author_facet	Jessica Roelands Raghvendra Mall Hossam Almeer Remy Thomas Mahmoud G. Mohamed Shahinaz Bedri Salha Bujassoum Al-Bader Kulsoom Junejo Elad Ziv Rosalyn W. Sayaman Peter J. K. Kuppen Davide Bedognetti Wouter Hendrickx Julie Decock
author_sort	Jessica Roelands
title	Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry
title_short	Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry
title_full	Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry
title_fullStr	Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry
title_full_unstemmed	Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry
title_sort	ancestry-associated transcriptomic profiles of breast cancer in patients of african, arab, and european ancestry
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b9ef27825e2f4d69a5e91d3295cb1212
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Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry

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