Racial disparities in the molecular landscape of cancer

Elisabeth I. Heath, Filipa Lynce, Joanne Xiu, Angela Ellerbrock, Sandeep K. Reddy, Elias Obeid, Stephen V. Liu, Aliccia Bollig-Fischer, Duska Separovic, Vanderwalde Ari

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background/Aim: African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. Materials and Methods: DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing. Additionally, we evaluated protein expression using immunohistochemistry. The Exome Aggregation Consortium Database was evaluated for known ethnicity associations. Results: Considering only pathogenic or presumed pathogenic mutations, as determined by the American College of Medical Genetics and Genomics guidelines, and using Bonferroni and Benjamini-Hochberg corrections for multiple comparisons, we found that CRC tumors from AA patients harbored significantly more mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) than those from CC patients. CRC tumors in AA patients also appeared to harbor more mutations of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin receptor, and neurofibromin 1 (NF1) than those from CC patients. In contrast, CRCs from AA patients were likely to carry fewer mutations of ataxia-telangiectasia mutated (ATM), as well as of proto-oncogene B-Raf (BRAF), including the V600E variant, than those from CC patients. Rates of immunohistochemical positivity for epidermal growth factor receptor (EGFR) and DNA topoisomerase 2-alpha (TOP2A) tended to be higher in CRCs from AA patients than in CC patients. In NSCLC adenocarcinoma, BRAF variants appeared to be more frequent in the AA than in the CC cohort, whereas in squamous cell lung carcinoma, programmed death-ligand 1 (PD-L1) expression tended to be lower in the AA than in CC group. Moreover, HGG tumors from AA patients showed a trend toward harboring more mutations of protein tyrosine phosphatase non-receptor 11 (PTPN11), than HGG tumors from the CC cohort. In contrast, mutations of phosphatase and tensin homolog (PTEN) and tumor protein 53 (TP53) appeared to be higher in HGG tumors in CC patients than in their AA counterparts. Conclusion: Our data revealed significant differences and trends in molecular signatures of the three cancer types in AA and CC cohorts. These findings imply that there may be differences in carcinogenesis between AA and CC patients and that race may be a factor that should be considered regarding cancer incidence and outcome.

Original languageEnglish (US)
Pages (from-to)2235-2240
Number of pages6
JournalAnticancer research
Volume38
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

African Americans
Neoplasms
Colorectal Neoplasms
Glioma
Mutation
Proto-Oncogenes
Non-Small Cell Lung Carcinoma
Non-Receptor Protein Tyrosine Phosphatases
Neurofibromin 1
MAP Kinase Kinase 1
Exome
Ataxia Telangiectasia
Type I DNA Topoisomerase
Incidence
Genomics
Phosphoric Monoester Hydrolases
Ethnic Groups
Epidermal Growth Factor Receptor
Paraffin
Formaldehyde

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Heath, E. I., Lynce, F., Xiu, J., Ellerbrock, A., Reddy, S. K., Obeid, E., ... Ari, V. (2018). Racial disparities in the molecular landscape of cancer. Anticancer research, 38(4), 2235-2240. https://doi.org/10.21873/anticanres.12466

Racial disparities in the molecular landscape of cancer. / Heath, Elisabeth I.; Lynce, Filipa; Xiu, Joanne; Ellerbrock, Angela; Reddy, Sandeep K.; Obeid, Elias; Liu, Stephen V.; Bollig-Fischer, Aliccia; Separovic, Duska; Ari, Vanderwalde.

In: Anticancer research, Vol. 38, No. 4, 01.04.2018, p. 2235-2240.

Research output: Contribution to journalArticle

Heath, EI, Lynce, F, Xiu, J, Ellerbrock, A, Reddy, SK, Obeid, E, Liu, SV, Bollig-Fischer, A, Separovic, D & Ari, V 2018, 'Racial disparities in the molecular landscape of cancer', Anticancer research, vol. 38, no. 4, pp. 2235-2240. https://doi.org/10.21873/anticanres.12466
Heath EI, Lynce F, Xiu J, Ellerbrock A, Reddy SK, Obeid E et al. Racial disparities in the molecular landscape of cancer. Anticancer research. 2018 Apr 1;38(4):2235-2240. https://doi.org/10.21873/anticanres.12466
Heath, Elisabeth I. ; Lynce, Filipa ; Xiu, Joanne ; Ellerbrock, Angela ; Reddy, Sandeep K. ; Obeid, Elias ; Liu, Stephen V. ; Bollig-Fischer, Aliccia ; Separovic, Duska ; Ari, Vanderwalde. / Racial disparities in the molecular landscape of cancer. In: Anticancer research. 2018 ; Vol. 38, No. 4. pp. 2235-2240.
@article{545d5a3134ce454a9b4f525f2664c830,
title = "Racial disparities in the molecular landscape of cancer",
abstract = "Background/Aim: African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. Materials and Methods: DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing. Additionally, we evaluated protein expression using immunohistochemistry. The Exome Aggregation Consortium Database was evaluated for known ethnicity associations. Results: Considering only pathogenic or presumed pathogenic mutations, as determined by the American College of Medical Genetics and Genomics guidelines, and using Bonferroni and Benjamini-Hochberg corrections for multiple comparisons, we found that CRC tumors from AA patients harbored significantly more mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) than those from CC patients. CRC tumors in AA patients also appeared to harbor more mutations of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin receptor, and neurofibromin 1 (NF1) than those from CC patients. In contrast, CRCs from AA patients were likely to carry fewer mutations of ataxia-telangiectasia mutated (ATM), as well as of proto-oncogene B-Raf (BRAF), including the V600E variant, than those from CC patients. Rates of immunohistochemical positivity for epidermal growth factor receptor (EGFR) and DNA topoisomerase 2-alpha (TOP2A) tended to be higher in CRCs from AA patients than in CC patients. In NSCLC adenocarcinoma, BRAF variants appeared to be more frequent in the AA than in the CC cohort, whereas in squamous cell lung carcinoma, programmed death-ligand 1 (PD-L1) expression tended to be lower in the AA than in CC group. Moreover, HGG tumors from AA patients showed a trend toward harboring more mutations of protein tyrosine phosphatase non-receptor 11 (PTPN11), than HGG tumors from the CC cohort. In contrast, mutations of phosphatase and tensin homolog (PTEN) and tumor protein 53 (TP53) appeared to be higher in HGG tumors in CC patients than in their AA counterparts. Conclusion: Our data revealed significant differences and trends in molecular signatures of the three cancer types in AA and CC cohorts. These findings imply that there may be differences in carcinogenesis between AA and CC patients and that race may be a factor that should be considered regarding cancer incidence and outcome.",
author = "Heath, {Elisabeth I.} and Filipa Lynce and Joanne Xiu and Angela Ellerbrock and Reddy, {Sandeep K.} and Elias Obeid and Liu, {Stephen V.} and Aliccia Bollig-Fischer and Duska Separovic and Vanderwalde Ari",
year = "2018",
month = "4",
day = "1",
doi = "10.21873/anticanres.12466",
language = "English (US)",
volume = "38",
pages = "2235--2240",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "4",

}

TY - JOUR

T1 - Racial disparities in the molecular landscape of cancer

AU - Heath, Elisabeth I.

AU - Lynce, Filipa

AU - Xiu, Joanne

AU - Ellerbrock, Angela

AU - Reddy, Sandeep K.

AU - Obeid, Elias

AU - Liu, Stephen V.

AU - Bollig-Fischer, Aliccia

AU - Separovic, Duska

AU - Ari, Vanderwalde

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background/Aim: African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. Materials and Methods: DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing. Additionally, we evaluated protein expression using immunohistochemistry. The Exome Aggregation Consortium Database was evaluated for known ethnicity associations. Results: Considering only pathogenic or presumed pathogenic mutations, as determined by the American College of Medical Genetics and Genomics guidelines, and using Bonferroni and Benjamini-Hochberg corrections for multiple comparisons, we found that CRC tumors from AA patients harbored significantly more mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) than those from CC patients. CRC tumors in AA patients also appeared to harbor more mutations of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin receptor, and neurofibromin 1 (NF1) than those from CC patients. In contrast, CRCs from AA patients were likely to carry fewer mutations of ataxia-telangiectasia mutated (ATM), as well as of proto-oncogene B-Raf (BRAF), including the V600E variant, than those from CC patients. Rates of immunohistochemical positivity for epidermal growth factor receptor (EGFR) and DNA topoisomerase 2-alpha (TOP2A) tended to be higher in CRCs from AA patients than in CC patients. In NSCLC adenocarcinoma, BRAF variants appeared to be more frequent in the AA than in the CC cohort, whereas in squamous cell lung carcinoma, programmed death-ligand 1 (PD-L1) expression tended to be lower in the AA than in CC group. Moreover, HGG tumors from AA patients showed a trend toward harboring more mutations of protein tyrosine phosphatase non-receptor 11 (PTPN11), than HGG tumors from the CC cohort. In contrast, mutations of phosphatase and tensin homolog (PTEN) and tumor protein 53 (TP53) appeared to be higher in HGG tumors in CC patients than in their AA counterparts. Conclusion: Our data revealed significant differences and trends in molecular signatures of the three cancer types in AA and CC cohorts. These findings imply that there may be differences in carcinogenesis between AA and CC patients and that race may be a factor that should be considered regarding cancer incidence and outcome.

AB - Background/Aim: African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. Materials and Methods: DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing. Additionally, we evaluated protein expression using immunohistochemistry. The Exome Aggregation Consortium Database was evaluated for known ethnicity associations. Results: Considering only pathogenic or presumed pathogenic mutations, as determined by the American College of Medical Genetics and Genomics guidelines, and using Bonferroni and Benjamini-Hochberg corrections for multiple comparisons, we found that CRC tumors from AA patients harbored significantly more mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) than those from CC patients. CRC tumors in AA patients also appeared to harbor more mutations of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin receptor, and neurofibromin 1 (NF1) than those from CC patients. In contrast, CRCs from AA patients were likely to carry fewer mutations of ataxia-telangiectasia mutated (ATM), as well as of proto-oncogene B-Raf (BRAF), including the V600E variant, than those from CC patients. Rates of immunohistochemical positivity for epidermal growth factor receptor (EGFR) and DNA topoisomerase 2-alpha (TOP2A) tended to be higher in CRCs from AA patients than in CC patients. In NSCLC adenocarcinoma, BRAF variants appeared to be more frequent in the AA than in the CC cohort, whereas in squamous cell lung carcinoma, programmed death-ligand 1 (PD-L1) expression tended to be lower in the AA than in CC group. Moreover, HGG tumors from AA patients showed a trend toward harboring more mutations of protein tyrosine phosphatase non-receptor 11 (PTPN11), than HGG tumors from the CC cohort. In contrast, mutations of phosphatase and tensin homolog (PTEN) and tumor protein 53 (TP53) appeared to be higher in HGG tumors in CC patients than in their AA counterparts. Conclusion: Our data revealed significant differences and trends in molecular signatures of the three cancer types in AA and CC cohorts. These findings imply that there may be differences in carcinogenesis between AA and CC patients and that race may be a factor that should be considered regarding cancer incidence and outcome.

UR - http://www.scopus.com/inward/record.url?scp=85045223031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045223031&partnerID=8YFLogxK

U2 - 10.21873/anticanres.12466

DO - 10.21873/anticanres.12466

M3 - Article

VL - 38

SP - 2235

EP - 2240

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 4

ER -