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 Pukkala; Pekka 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

doi:10.1002/ijc.31076

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

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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 language	English
Pages (from-to)	540-546
Number of pages	7
Journal	International Journal of Cancer
Volume	142
Issue number	3
DOIs	https://doi.org/10.1002/ijc.31076
State	Published - 1 Feb 2018
Externally published	Yes

Keywords

colorectal cancer
genetic predisposition to disease
genome-wide association study
single-nucleotide polymorphism

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10.1002/ijc.31076

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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, P. J., Tuupanen, S., Gylfe, A. E., Hänninen, U. A., Cajuso, T., Kondelin, J., Sarin, A. P., ... Aaltonen, L. A. (2018). Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci. International Journal of Cancer, 142(3), 540-546. https://doi.org/10.1002/ijc.31076

@article{1bca30f1d54e41ec9fb1802da2e74287,

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

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.",

keywords = "colorectal cancer, genetic predisposition to disease, genome-wide association study, single-nucleotide polymorphism",

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

note = "Publisher Copyright: {\textcopyright} 2017 UICC",

year = "2018",

month = feb,

day = "1",

doi = "10.1002/ijc.31076",

language = "English",

volume = "142",

pages = "540--546",

journal = "International Journal of Cancer",

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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, AP, Pukkala, E, Jousilahti, P, Salomaa, V, Ripatti, S, Palotie, A, Järvinen, H, Renkonen-Sinisalo, L, Lepistö, A, Böhm, J, Mecklin, JP, 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 2018, 'Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci', International Journal of Cancer, vol. 142, no. 3, pp. 540-546. https://doi.org/10.1002/ijc.31076

TY - JOUR

T1 - Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci

AU - Tanskanen, Tomas

AU - van den Berg, Linda

AU - Välimäki, Niko

AU - Aavikko, Mervi

AU - Ness-Jensen, Eivind

AU - Hveem, Kristian

AU - Wettergren, Yvonne

AU - Bexe Lindskog, Elinor

AU - Tõnisson, Neeme

AU - Metspalu, Andres

AU - Silander, Kaisa

AU - Orlando, Giulia

AU - Law, Philip J.

AU - Tuupanen, Sari

AU - Gylfe, Alexandra E.

AU - Hänninen, Ulrika A.

AU - Cajuso, Tatiana

AU - Kondelin, Johanna

AU - Sarin, Antti Pekka

AU - Pukkala, Eero

AU - Jousilahti, Pekka

AU - Salomaa, Veikko

AU - Ripatti, Samuli

AU - Palotie, Aarno

AU - Järvinen, Heikki

AU - Renkonen-Sinisalo, Laura

AU - Lepistö, Anna

AU - Böhm, Jan

AU - Mecklin, Jukka Pekka

AU - Al-Tassan, Nada A.

AU - Palles, Claire

AU - Martin, Lynn

AU - Barclay, Ella

AU - Tenesa, Albert

AU - Farrington, Susan M.

AU - Timofeeva, Maria N.

AU - Meyer, Brian F.

AU - Wakil, Salma M.

AU - Campbell, Harry

AU - Smith, Christopher G.

AU - Idziaszczyk, Shelley

AU - Maughan, Tim S.

AU - Kaplan, Richard

AU - Kerr, Rachel

AU - Kerr, David

AU - Buchanan, Daniel D.

AU - Win, Aung K.

AU - Hopper, John

AU - Jenkins, Mark A.

AU - Newcomb, Polly A.

AU - Gallinger, Steve

AU - Conti, David

AU - Schumacher, Fredrick R.

AU - Casey, Graham

AU - Cheadle, Jeremy P.

AU - Dunlop, Malcolm G.

AU - Tomlinson, Ian P.

AU - Houlston, Richard S.

AU - Palin, Kimmo

AU - Aaltonen, Lauri A.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - colorectal cancer

KW - genetic predisposition to disease

KW - genome-wide association study

KW - single-nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=85031408086&partnerID=8YFLogxK

U2 - 10.1002/ijc.31076

DO - 10.1002/ijc.31076

M3 - Article

C2 - 28960316

AN - SCOPUS:85031408086

SN - 0020-7136

VL - 142

SP - 540

EP - 546

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 3

ER -

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

Abstract

Keywords

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