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Int J Cancer DOI:10.1002/ijc.31076

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

Publication TypeJournal Article
Year of Publication2018
AuthorsTanskanen, T, van den Berg, L, Välimäki, N, Aavikko, M, Ness-Jensen, E, Hveem, K, Wettergren, Y, Lindskog, EBexe, Tõnisson, N, Metspalu, A, Silander, K, Orlando, G, Law, PJ, Tuupanen, S, Gylfe, AE, Hänninen, UA, Cajuso, T, Kondelin, J, Sarin, A-P, Pukkala, E, Jousilahti, P, Salomaa, V, Ripatti, S, Palotie, A, Järvinen, H, Renkonen-Sinisalo, L, Lepistö, A, Böhm, J, Mecklin, J-P, Al-Tassan, NA, Palles, C, Martin, L, Barclay, E, Tenesa, A, Farrington, SM, Timofeeva, MN, Meyer, BF, Wakil, SM, Campbell, H, Smith, CG, Idziaszczyk, S, Maughan, TS, Kaplan, R, Kerr, R, Kerr, D, Buchanan, DD, Win, AK, Hopper, J, Jenkins, MA, Newcomb, PA, Gallinger, S, Conti, D, Schumacher, FR, Casey, G, Cheadle, JP, Dunlop, MG, Tomlinson, IP, Houlston, RS, Palin, K, Aaltonen, LA
JournalInt J Cancer
Volume142
Issue3
Pages540-546
Date Published2018 02 01
ISSN1097-0215
KeywordsCase-Control Studies, Cohort Studies, Colorectal Neoplasms, Estonia, Finland, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Registries
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 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 × 10 ; 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.

DOI10.1002/ijc.31076
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28960316?dopt=Abstract

Alternate JournalInt. J. Cancer
PubMed ID28960316
PubMed Central IDPMC6383773
Grant ListG1001799 / / Medical Research Council / United Kingdom
U01 CA074799 / CA / NCI NIH HHS / United States
MC_PC_U127527198 / / Medical Research Council / United Kingdom
U24 CA074783 / CA / NCI NIH HHS / United States
U24 CA074794 / CA / NCI NIH HHS / United States
MR/K014781/1 / / Medical Research Council / United Kingdom
U24 CA074806 / CA / NCI NIH HHS / United States
U24 CA097735 / CA / NCI NIH HHS / United States
U01 CA074794 / CA / NCI NIH HHS / United States
MR/N01104X/1 / / Medical Research Council / United Kingdom
U01 CA167551 / CA / NCI NIH HHS / United States
R01 CA143237 / CA / NCI NIH HHS / United States
MR/K018647/1 / / Medical Research Council / United Kingdom
MC_UU_12023/3 / / Medical Research Council / United Kingdom
13154 / / Cancer Research UK / United Kingdom
U01 CA097735 / CA / NCI NIH HHS / United States
UM1 CA167551 / CA / NCI NIH HHS / United States
U01 CA122839 / CA / NCI NIH HHS / United States
U01 CA074783 / CA / NCI NIH HHS / United States
U24 CA074799 / CA / NCI NIH HHS / United States
U01 CA074806 / CA / NCI NIH HHS / United States
U24 CA074800 / CA / NCI NIH HHS / United States
U01 CA074800 / CA / NCI NIH HHS / United States
U19 CA148107 / CA / NCI NIH HHS / United States