Ancestry Influences on the Molecular Presentation of Tumours

Ch, Li; Haider, Syed; Boutros, PC

doi:10.1101/2020.08.02.233528

Cited by 2 publications

(5 citation statements)

References 67 publications

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“…53,54 The prior TCGA pan-cancer studies defined their cohorts by genetic ancestry rather than self-identification and did not stratify by HPV status. [17][18][19] Still, they reported findings consistent with our study, including differences in chromosomal instability and PI3K pathway. The study by Guerrero-Preston et al compared selfidentifying Black and non-Latinx White HNSCC patients treated at Johns Hopkins University.…”

Section: Discussionsupporting

confidence: 89%

“…The prior TCGA pan‐cancer studies defined their cohorts by genetic ancestry rather than self‐identification and did not stratify by HPV status 17–19 . Still, they reported findings consistent with our study, including differences in chromosomal instability and PI3K pathway.…”

Section: Discussionsupporting

confidence: 82%

“…Earlier studies of a Johns Hopkins University HNSCC cohort and pan‐cancer cohorts in The Cancer Genome Atlas (TCGA) have found differences between tumors of African American and White patients in somatic mutations, chromosomal instability, protein abundances, immune signatures, and DNA methylation 8,17–19 . The TCGA HNSCC study provided comprehensive multiplatform molecular data on 515 patient samples.…”

Section: Introductionmentioning

confidence: 99%

“…Earlier studies of a Johns Hopkins University HNSCC cohort and pan-cancer cohorts in The Cancer Genome Atlas (TCGA) have found differences between tumors of African American and White patients in somatic mutations, chromosomal instability, protein abundances, immune signatures, and DNA methylation. 8,[17][18][19] The TCGA HNSCC study provided comprehensive multiplatform molecular data on 515 patient samples. We have curated racial and ethnic data into REGs to carry out a comparison of clinical characteristics and tumor molecular features, using methods distinct from previously published literature.…”

Section: Introductionmentioning

confidence: 99%

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Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer

et al. 2022

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Background Numerous studies of head and neck squamous cell carcinoma (HNSCC) have demonstrated disparate outcomes by race and ethnicity. Beyond known associations with socioeconomic variables, whether these are also associated with differences in tumor molecular composition has thus far been poorly explored. Methods We downloaded clinical and multiplatform molecular data from The Cancer Genome Atlas and other published studies. These were compared between non‐Hispanic Black (n = 43) and White (n = 354) patients with non‐HPV‐related tumors, using multivariable models. Publicly available validation cohorts were used. Results Black patients had poorer progression‐free survival than White patients. Tumors of Black patients had greater copy number aberrations, and increased SFRP1 methylation and miRNA‐mediated PRG4 silencing associated with poor survival. PI3K/AkT/mTOR pathway proteins were differentially expressed. Conclusions There are molecular differences between tumors of Black and White patients that may partially account for differences in survival. These may inform targeted treatment decisions to achieve equitable outcomes.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer

et al. 2022

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“…7b). Second, ancestral 26 and geographic data of patients should be included in molecular profiling of cancers. Lastly, the inclusion of ethnic disparity in cancer studies would need to properly address admixture in a sampling cohort, with too low ancestral cut-off appearing to create highly admixed, but similar ancestry among individuals, therefore discouraging ethnically diverse samples.…”

Section: Global Molecular Subtypesmentioning

confidence: 99%

African-specific prostate cancer molecular taxonomy

Hayes¹,

Jaratlerdsiri²,

Jue³

et al. 2021

Preprint

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Prostate cancer is characterised by significant global disparity; mortality rates in Sub-Saharan Africa are double to quadruple those in Eurasia1. Hypothesising unknown interplay between genetic and non-genetic factors, tumour genome profiling envisages contributing mutational processes2,3. Through whole-genome sequencing of treatment-naïve prostate cancer from 183 ethnically/globally distinct patients (African versus European), we generate the largest cancer genomics resource for Sub-Saharan Africa. Identifying ~2 million somatic variants, Africans carried the greatest burden. We describe a new molecular taxonomy using all mutational types and ethno-geographic identifiers, including Asian. Defined as Global Mutational Subtypes (GMS) A–D, although Africans presented within all subtypes, we found GMS-B to be ‘African-specific’ and GMS-D ‘African-predominant’, including Admixed and European Africans. Conversely, Europeans from Australia, Africa and Brazil predominated within ‘mutationally-quiet’ and ethnically/globally ‘universal’ GMS-A, while European Australians shared a higher mutational burden with Africans in GMS-C. GMS predicts clinical outcomes; reconstructing cancer timelines suggests four evolutionary trajectories with different mutation rates (GMS-A, low 0.968/year versus D, highest 1.315/year). Our data suggest both common genetic factors across extant populations and regional environmental factors contributing to carcinogenesis, analogous to gene-environment interaction defined here as a different effect of an environmental surrounding in persons with different ancestries or vice versa. We anticipate GMS acting as a proxy to intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.

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Ancestry Influences on the Molecular Presentation of Tumours

Cited by 2 publications

References 67 publications

Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer

Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer

African-specific prostate cancer molecular taxonomy

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