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Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.

  • Author(s): Rashkin, Sara R
  • Graff, Rebecca E
  • Kachuri, Linda
  • Thai, Khanh K
  • Alexeeff, Stacey E
  • Blatchins, Maruta A
  • Cavazos, Taylor B
  • Corley, Douglas A
  • Emami, Nima C
  • Hoffman, Joshua D
  • Jorgenson, Eric
  • Kushi, Lawrence H
  • Meyers, Travis J
  • Van Den Eeden, Stephen K
  • Ziv, Elad
  • Habel, Laurel A
  • Hoffmann, Thomas J
  • Sakoda, Lori C
  • Witte, John S
  • et al.
Abstract

Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.

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