Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.
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Date
2018-02-01Author
Tanskanen, T
van den Berg, L
Välimäki, N
Aavikko, M
Ness-Jensen, E
Hveem, K
Wettergren, Y
Bexe Lindskog, E
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Colorectal Neoplasms
Genetic Predisposition to Disease
Registries
Case-Control Studies
Cohort Studies
Polymorphism, Single Nucleotide
Estonia
Finland
Genome-Wide Association Study
Research team
Cancer Genomics
Language
eng
Date accepted
2017-09-01
License start date
2018-02
Citation
International journal of cancer, 2018, 142 (3), pp. 540 - 546
Publisher
WILEY