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Roelands J, Mall R, Almeer H, et al. Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry. NPJ Breast Cancer. 2021;7(1):10doi: 10.1038/s41523-021-00215-x.
Roelands, J., Mall, R., Almeer, H., Thomas, R., Mohamed, M. G., Bedri, S., Al-Bader, S. B., Junejo, K., Ziv, E., Sayaman, R. W., Kuppen, P. J. K., Bedognetti, D., Hendrickx, W., & Decock, J. (2021). Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry. NPJ breast cancer, 7(1), 10. https://doi.org/10.1038/s41523-021-00215-x
Roelands, Jessica, et al. "Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry." NPJ breast cancer vol. 7,1 (2021): 10. doi: https://doi.org/10.1038/s41523-021-00215-x
Roelands J, Mall R, Almeer H, Thomas R, Mohamed MG, Bedri S, Al-Bader SB, Junejo K, Ziv E, Sayaman RW, Kuppen PJK, Bedognetti D, Hendrickx W, Decock J. Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry. NPJ Breast Cancer. 2021 Feb 08;7(1):10. doi: 10.1038/s41523-021-00215-x. PMID: 33558495; PMCID: PMC7870839.
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NPJ Breast Cancer. 2021 Feb 08;7(1):10. doi: 10.1038/s41523-021-00215-x.

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

NPJ breast cancer

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

Affiliations

  1. Functional Cancer Omics Lab, Cancer Group, Research Branch, Sidra Medicine, Doha, Qatar.
  2. Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
  3. Qatar Computing Research Institute (QCRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.
  4. Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.
  5. Women's Hospital, Hamad Medical Corporation, Doha, Qatar.
  6. Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy.
  7. Weill Cornell Medicine-Qatar, Doha, Qatar.
  8. National Center for Cancer Care and Research (NCCCR), Hamad General Hospital, Doha, Qatar.
  9. General Surgery Department, Hamad General Hospital, Doha, Qatar.
  10. Department of Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
  11. Department of Population Sciences, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  12. Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
  13. Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy. [email protected].
  14. Cancer Immunogenetics Lab, Cancer Group, Research Branch, Sidra Medicine, Doha, Qatar. [email protected].
  15. College of Health and Life Sciences (CHLS), Hamad bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar. [email protected].
  16. Functional Cancer Omics Lab, Cancer Group, Research Branch, Sidra Medicine, Doha, Qatar. [email protected].
  17. College of Health and Life Sciences (CHLS), Hamad bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar. [email protected].
  18. Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar. [email protected].
  19. College of Health and Life Sciences (CHLS), Hamad bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar. [email protected].

PMID: 33558495 PMCID: PMC7870839 DOI: 10.1038/s41523-021-00215-x

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.

References

  1. Oncoimmunology. 2017 Feb 6;6(2):e1253654 - PubMed
  2. Bioinformatics. 2010 Jun 15;26(12):1572-3 - PubMed
  3. Cell. 2015 Jan 15;160(1-2):48-61 - PubMed
  4. BMC Bioinformatics. 2013 Jan 16;14:7 - PubMed
  5. J Natl Cancer Inst. 2009 Jul 15;101(14):984-92 - PubMed
  6. JAMA Oncol. 2016 Aug 1;2(8):1070-4 - PubMed
  7. Cancer Immunol Res. 2016 Jul;4(7):600-10 - PubMed
  8. PLoS One. 2009;4(2):e4531 - PubMed
  9. Br J Cancer. 2010 Jan 19;102(2):369-75 - PubMed
  10. NPJ Breast Cancer. 2019 Sep 9;5:30 - PubMed
  11. Genome Biol. 2020 Feb 20;21(1):42 - PubMed
  12. BMC Bioinformatics. 2011 Dec 17;12:480 - PubMed
  13. Oncotarget. 2017 Dec 23;9(2):2697-2704 - PubMed
  14. Sci Rep. 2015 Aug 27;5:13526 - PubMed
  15. Comput Math Methods Med. 2013;2013:873595 - PubMed
  16. J Clin Oncol. 2014 Sep 20;32(27):2959-66 - PubMed
  17. J Clin Oncol. 2015 Dec 20;33(36):4267-76 - PubMed
  18. J Exp Clin Cancer Res. 2018 Dec 29;37(1):327 - PubMed
  19. Ann Surg Oncol. 2017 Oct;24(10):2869-2875 - PubMed
  20. Cancer Cell. 2020 May 11;37(5):639-654.e6 - PubMed
  21. Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):127-34 - PubMed
  22. J Clin Oncol. 2010 Jan 1;28(1):105-13 - PubMed
  23. J Clin Oncol. 2013 Mar 1;31(7):860-7 - PubMed
  24. J Immunother Cancer. 2020 Apr;8(1): - PubMed
  25. Oncotarget. 2016 Nov 29;7(48):79274-79291 - PubMed
  26. Transl Oncol. 2018 Apr;11(2):311-329 - PubMed
  27. Carcinogenesis. 2016 Sep;37(9):870-877 - PubMed
  28. JAMA Oncol. 2017 Dec 1;3(12):1654-1662 - PubMed
  29. Nat Commun. 2018 Oct 16;9(1):4181 - PubMed
  30. PLoS One. 2013 Nov 18;8(11):e71915 - PubMed
  31. Emerg Top Life Sci. 2017 Dec 12;1(5):429-445 - PubMed
  32. Breast Cancer Res Treat. 2017 Feb;161(3):491-499 - PubMed
  33. Breast Cancer Res Treat. 2014 Apr;144(3):689-99 - PubMed
  34. Breast Cancer Res Treat. 2013 Jun;139(2):497-506 - PubMed
  35. J Natl Cancer Inst. 2010 Aug 4;102(15):1178-87 - PubMed
  36. PLoS One. 2012;7(11):e49359 - PubMed
  37. Bioinformatics. 2014 Oct;30(19):2811-2 - PubMed
  38. Cell Stem Cell. 2007 Nov;1(5):555-67 - PubMed
  39. Biology (Basel). 2012 Dec 14;1(3):895-905 - PubMed
  40. Oncotarget. 2018 Feb 7;9(14):11677-11690 - PubMed
  41. Br J Cancer. 2014 Jan 7;110(1):230-41 - PubMed
  42. J Clin Oncol. 2019 Mar 1;37(7):559-569 - PubMed
  43. Breast. 2016 Dec;30:39-46 - PubMed
  44. EMBO Mol Med. 2013 Feb;5(2):264-79 - PubMed
  45. Oncoimmunology. 2016 Oct 18;5(12):e1240857 - PubMed
  46. Breast Cancer Res. 2019 Feb 21;21(1):29 - PubMed
  47. Bioinformatics. 2016 Sep 15;32(18):2847-9 - PubMed
  48. J Clin Oncol. 2009 Mar 10;27(8):1160-7 - PubMed
  49. Cell Syst. 2015 Dec 23;1(6):417-425 - PubMed
  50. Cancers (Basel). 2018 Dec 14;10(12): - PubMed
  51. Oncol Nurs Forum. 2013 Sep;40(5):490-500 - PubMed
  52. J Clin Oncol. 2009 Sep 20;27(27):4515-21 - PubMed
  53. Nucleic Acids Res. 2019 May 7;47(8):e47 - PubMed
  54. Immunity. 2018 Apr 17;48(4):812-830.e14 - PubMed
  55. Nature. 2009 Nov 5;462(7269):108-12 - PubMed
  56. Lancet Oncol. 2018 Jan;19(1):40-50 - PubMed
  57. Nature. 2017 Jan 12;541(7636):233-236 - PubMed
  58. BMC Cancer. 2009 Sep 01;9:307 - PubMed
  59. Cell. 2018 Apr 5;173(2):400-416.e11 - PubMed
  60. Breast Cancer Res Treat. 2019 May;175(1):247-259 - PubMed
  61. J Clin Nurs. 2002 Nov;11(6):723 - PubMed
  62. Curr Opin Oncol. 2015 Nov;27(6):433-44 - PubMed
  63. JAMA Surg. 2017 May 1;152(5):485-493 - PubMed
  64. JAMA. 2015 Jan 13;313(2):165-73 - PubMed
  65. PLoS One. 2013 Dec 04;8(12):e82460 - PubMed
  66. Breast Cancer Res Treat. 2011 Feb;126(1):215-20 - PubMed
  67. Emerg Top Life Sci. 2017 Dec 12;1(5):411-419 - PubMed
  68. Cell Cycle. 2012 Jan 15;11(2):367-76 - PubMed
  69. Immunity. 2013 Oct 17;39(4):782-95 - PubMed
  70. Ann Surg Oncol. 2015 Mar;22(3):874-82 - PubMed
  71. Br J Cancer. 2008 Jan 29;98(2):277-81 - PubMed
  72. J Clin Oncol. 2015 Nov 1;33(31):3621-7 - PubMed
  73. Nat Methods. 2014 Jun;11(6):599-600 - PubMed
  74. Front Biosci (Landmark Ed). 2017 Mar 1;22:1221-1246 - PubMed
  75. Nat Methods. 2015 Apr;12(4):357-60 - PubMed
  76. Oncogene. 2014 Jan 9;33(2):148-56 - PubMed
  77. Cell Death Differ. 2014 Jan;21(1):15-25 - PubMed
  78. J Clin Oncol. 2006 Mar 20;24(9):1342-9 - PubMed
  79. Br J Cancer. 2018 Nov;119(11):1383-1391 - PubMed
  80. J Natl Cancer Inst. 2018 Feb 1;110(2): - PubMed
  81. Nat Commun. 2013;4:2612 - PubMed
  82. Oncotarget. 2015 May 10;6(13):11231-41 - PubMed
  83. Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):714-24 - PubMed
  84. BMC Res Notes. 2012 May 22;5:248 - PubMed
  85. JAMA. 2006 Jun 7;295(21):2492-502 - PubMed
  86. Cancer Res. 2018 Mar 1;78(5):1140-1154 - PubMed
  87. Cancer Med. 2017 Mar;6(3):526-536 - PubMed
  88. Cancer. 2020 Feb 15;126(4):800-807 - PubMed
  89. J Clin Invest. 2011 Jul;121(7):2750-67 - PubMed
  90. Cancer. 2012 Mar 1;118(5):1334-44 - PubMed
  91. Clin Cancer Res. 2010 Feb 15;16(4):1272-80 - PubMed
  92. Transl Oncol. 2013 Dec 01;6(6):757-65 - PubMed

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