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Genome‐wide association study and meta‐analysis in Northern European populations replicate multiple colorectal cancer risk loci
Author(s) -
Tanskanen Tomas,
van den Berg Linda,
Välimäki Niko,
Aavikko Mervi,
NessJensen Eivind,
Hveem Kristian,
Wettergren Yvonne,
Bexe Lindskog Elinor,
Tõnisson Neeme,
Metspalu Andres,
Silander Kaisa,
Orlando Giulia,
Law Philip J.,
Tuupanen Sari,
Gylfe Alexandra E.,
Hänninen Ulrika A.,
Cajuso Tatiana,
Kondelin Johanna,
Sarin AnttiPekka,
Pukkala Eero,
Jousilahti Pekka,
Salomaa Veikko,
Ripatti Samuli,
Palotie Aarno,
Järvinen Heikki,
RenkonenSinisalo Laura,
Lepistö Anna,
Böhm Jan,
Mecklin JukkaPekka,
AlTassan 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 A.
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31076
Subject(s) - genome wide association study , single nucleotide polymorphism , biology , genetics , genetic association , colorectal cancer , population , snp , cancer , genotype , medicine , gene , environmental health
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.