{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Cancer Genomics"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001006425"],"host":["EGA"],"description":["EGA study EGAS00001006425"],"dataset_title":["Garvan/St Vincent’s Prostate Cancer Tissue and Data","Southern African Prostate Cancer Study (SAPCS) Ethnic Disparity"],"category":["restricted"],"repository":["EGA"],"additional_accession":[]},"is_claimable":false,"name":"Prostate cancer ancestral genomic disparity","description":"Prostate cancer is characterised by significant global disparity; mortality rates in SubSaharan Africa are double to quadruple those in Eurasia. Hypothesising unknown interplay between genetic and non-genetic factors, tumour genome profiling envisages contributing mutational processes. 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 ethno39 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 GMS45 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.","dates":{"updated":"2022-07-20 11:10:43"},"accession":"EGAS00001006425","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001009067","EGAD00001009066","EGAC00001002768","EGAC00001002769"]}}