Genomic ancestry in kidney cancer: Correlations with clinical and molecular features Journal Article
| Authors: | Kotecha, R. R.; Knezevic, A.; Arora, K.; Bandlamudi, C.; Kuo, F.; Carlo, M. I.; Fitzgerald, K. N.; Feldman, D. R.; Shah, N. J.; Reznik, E.; Hakimi, A. A.; Carrot-Zhang, J.; Mandelker, D.; Berger, M.; Lee, C. H.; Motzer, R. J.; Voss, M. H. |
| Article Title: | Genomic ancestry in kidney cancer: Correlations with clinical and molecular features |
| Abstract: | Introduction: Genetic ancestry (GA) refers to population hereditary patterns that contribute to phenotypic differences seen among race/ethnicity groups, and differences among GA groups may highlight unique biological determinants that add to our understanding of health care disparities. Methods: A retrospective review of patients with renal cell carcinoma (RCC) was performed and correlated GA with clinicopathologic, somatic, and germline molecular data. All patients underwent next-generation sequencing of normal and tumor DNA using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, and contribution of African (AFR), East Asian (EAS), European (EUR), Native American, and South Asian (SAS) ancestry was inferred through supervised ADMIXTURE. Molecular data was compared across GA groups by Fisher exact test and Kruskal–Wallis test. Results: In 953 patients with RCC, the GA distribution was: EUR (78%), AFR (4.9%), EAS (2.5%), SAS (2%), Native American (0.2%), and Admixed (12.2%). GA distribution varied by tumor histology and international metastatic RCC database consortium disease risk status (intermediate-poor: EUR 58%, AFR 88%, EAS 74%, and SAS 73%). Pathogenic/likely pathogenic germline variants in cancer-predisposition genes varied (16% EUR, 23% AFR, 8% EAS, and 0% SAS), and most occurred in CHEK2 in EUR (3.1%) and FH in AFR (15.4%). In patients with clear cell RCC, somatic alteration incidence varied with significant enrichment in BAP1 alterations (EUR 17%, AFR 50%, SAS 29%; p =.01). Comparing AFR and EUR groups within The Cancer Genome Atlas, significant differences were identified in angiogenesis and inflammatory pathways. Conclusion: Differences in clinical and molecular data by GA highlight population-specific variations in patients with RCC. Exploration of both genetic and nongenetic variables remains critical to optimize efforts to overcome health-related disparities. © 2023 American Cancer Society. |
| Keywords: | adult; cancer survival; controlled study; human tissue; aged; major clinical study; overall survival; somatic mutation; genetics; clinical feature; cancer risk; gene; cancer susceptibility; incidence; inflammation; cohort analysis; angiogenesis; genetics, population; retrospective study; histology; renal cell carcinoma; kidney neoplasms; self report; kidney tumor; carcinoma, renal cell; mammalian target of rapamycin; genomics; checkpoint kinase 2; kidney cancer; molecular biology; glycolysis; oxidative phosphorylation; ethnicity; hla antigen; american indian; african; genetic correlation; clear cell renal cell carcinoma; bap1 gene; population genetics; european; tumor metabolism; chek2 gene; high throughput sequencing; east asian; south asian; humans; human; male; female; article; molecular feature; genomic ancestry; fh gene; people of mixed ancestry; population genomics |
| Journal Title: | Cancer |
| Volume: | 130 |
| Issue: | 5 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2024-03-01 |
| Start Page: | 692 |
| End Page: | 701 |
| Language: | English |
| DOI: | 10.1002/cncr.35074 |
| PUBMED: | 37864521 |
| PROVIDER: | scopus |
| PMCID: | PMC11220722 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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