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

Tanskanen, Tomas; Van Den Berg, Linda; Välimäki, Niko; Aavikko, Mervi; Ness-Jensen, Eivind; Hveem, Kristian; Wettergren, Yvonne; Lindskog, Elinor Bexe; Tönisson, Neeme; Metspalu, Andres; Silander, Kaisa; Orlando, Giulia; Law, Philip J.; Tuupanen, Sari; Gylfe, Alexandra E.; Hänninen, Ulrika A.; Cajuso, Tatiana; Kondelin, Johanna; Sarin, Antti-Pekka; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A.; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan M.; Timofeeva, Maria N.; Meyer, Brian F; Wakil, Salma M.; Campbell, Harry; Smith, Christopher G.; Idziaszczyk, Shelley; Maughan, Tim S.; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D.; Win, Aung K.; Hopper, John; Jenkins, Mark A.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fredrick R.; Casey, Graham; Cheadle, Jeremy P.; Dunlop, Malcolm G.; Tomlinson, Ian P; Houlston, Richard S.; Palin, Kimmo; Aaltonen, Lauri
Journal article, Peer reviewed
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URI
http://hdl.handle.net/11250/2483441
Date
2018
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  • Institutt for samfunnsmedisin og sykepleie [4227]
  • Publikasjoner fra CRIStin - NTNU [41957]
Original version
International Journal of Cancer. 2018, 142 (3), 540-546.   10.1002/ijc.31076
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.
Publisher
Wiley
Journal
International Journal of Cancer

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