Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci

Tomas Tanskanen, Linda van den Berg, Niko Välimäki, Mervi Aavikko, Eivind Ness-Jensen, Kristian Hveem, Yvonne Wettergren, Elinor Bexe Lindskog, Neeme Tõnisson, Andres Metspalu, Kaisa Silander, Giulia Orlando, Philip J Law, Sari Tuupanen, Alexandra E Gylfe, Ulrika A Hänninen, Tatiana Cajuso, Johanna Kondelin, Antti-Pekka Sarin, Eero PukkalaPekka Jousilahti, Veikko Salomaa, Samuli Ripatti, Aarno Palotie, Heikki Järvinen, Laura Renkonen-Sinisalo, Anna Lepistö, Jan Böhm, Jukka-Pekka Mecklin, Nada A Al-Tassan, Claire Palles, Lynn Martin, Ella Barclay, Albert Tenesa, Susan M Farrington, Maria N Timofeeva, Brian F Meyer, Salma M Wakil, Harry Campbell, Christopher G Smith, Shelley Idziaszczyk, Tim S Maughan, Richard Kaplan, Rachel Kerr, David Kerr, Daniel D Buchanan, Aung K Win, John Hopper, Mark A Jenkins, Polly A Newcomb, Steve Gallinger, David Conti, Fredrick R Schumacher, Graham Casey, Jeremy P Cheadle, Malcolm G Dunlop, Ian P Tomlinson, Richard S Houlston, Kimmo Palin, Lauri A Aaltonen

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 × 10-4 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 × 10-9 ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.

Original languageEnglish
Pages (from-to)540-546
Number of pages7
JournalInternational Journal of Cancer
Volume142
Issue number3
Early online date12 Oct 2017
DOIs
Publication statusPublished - 9 Dec 2018

Keywords

  • Case-Control Studies
  • Cohort Studies
  • Colorectal Neoplasms
  • Estonia
  • Finland
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Polymorphism, Single Nucleotide
  • Registries
  • Journal Article
  • Meta-Analysis

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