Abstract
Abstract Introduction Prostate cancer is the most common cancer in men and there is racial disparity in prostate cancer incidence and mortality globally, with greater disease burden in men of African ancestry, followed by European ancestry and least in men of Asian ancestry. The etiology of prostate cancer is not fully understood but includes genetic and environmental factors. Present day non-Africans are reported to have introgressed DNA from Neanderthal and Denisovan ancestors. Over 170 prostate cancer associated single nucleotide polymorphisms (SNPs) have been identified from several genome-wide association studies (GWAS), with SNPS on chromosomes 2, 8 and 22 reported as showing variation between African and non-African men with prostate cancer. We performed analysis of prostate cancer associated SNPs on chromosomes 2, 8 and 22 to determine if DNA introgression could explain the racial variation. Methods We obtained data on prostate cancer associated SNPs from the GWAS catalog (https://www.ebi.ac.uk/gwas) and from reports that were not included in the catalog. Using an Ancient Genome Browser provided by the Max Plank Institute (https://www.eva.mpg.de/genetics/genome-projects/neandertal/index.html), we determined whether SNPs on chromosomes 2, 8 and 22 were present in African, Neanderthal or Denisovan genomes. Based on the results, we inferred that SNPs were introgressed if they were present in Neanderthal or Denisovan genomes but absent from African genomes. Results 49, 59 and 17 prostate cancer SNPs were reported in chromosomes 2, 8 and 22 respectively. 23/49 in ch2, 25/59 in c 8 and 9/17 in ch22 were present in in Neanderthal and or Denisovan genomes. SNPs in ch2 (rs13403657, rs12621278) and ch8 (rs7825414) were present in Neanderthal or Denisovan genomes but absent in African genomes. These SNPs lie in regions that have previously been reported to harbour introgressd DNA. Conclusion Our analyses identified prostate cancer associated SNPs that are likely to have been introgressed into present day non-Africans by extinct Neanderthal and Denisovan ancestors. Phenotypic changes caused by introgressed DNA could be contributing to racial disparities in prostate cancer in present day humans. Citation Format: Evi O. Useh, Suresh Venugopal, Chidi N. Molokwu. Exploring the contribution of introgressed ancient DNA to prostate cancer racial disparity [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-192.
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