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Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Law PJ; Timofeeva M; Fernandez-Rozadilla C; Timofeeva A; Broderick P; Studd J; Fernandez-Tajes J; Farrington S; Svinti V; Palles C; Orlando G; Sud A; Holroyd A; Penegar S; Theodoratou E; Vaughan-Shaw P; Campbell H; Zgaga L; Hayward C; Campbell A; Harris S; Deary IJ; Starr O; Gatcombe L; Pinna M; Briggs S; Martin L; Jaeger E; Sharma-Oates A; East J; Leedham S; Arnold R; Johnstone E; Wang H; Kerr D; Kerr R; Maughan T; Kaplan R; Al-Tassan N; Palin K; Hanninen UA; Cajuso T; Tanskanen T; Kondelin J; Kaasinen E; Sarin AP; Eriksson JG; Rissanen H; Knekt P; Pukkala E; Jousilahti P; Salomaa V; Ripatti S; Palotie A; Renkonen-Sinisalo L; Lepisto A; Bohm J; Mecklin JP; Buchanan DD; Win AK; Hopper J; Jenkins ME; Lindor NM; Newcomb PA; Gallinger S; Duggan D; Casey G; Hoffmann P; Nothen MM; Jockel KH; Easton DF; Pharoah PDP; Peto J; Canzian F; Swerdlow A; Eeles RA; Kote-Jarai Z; Muir K; Pashayan N; Harkin A; Allan K; McQueen J; Paul J; Iveson T; Saunders M; Butterbach K; Chang-Claude J; Hoffmeister M; Brenner H; Kirac I; Matosevic P; Hofer P; Brezina S; Gsur A; Cheadle JP; Aaltonen LA; Tomlinson I; Houlston RS; Dunlop MG; Henderson BE; Haiman CA; Schumacher FR; Al Olama AA; Benlloch S; Berndt SI; Conti DV; Wiklund F; Chanock S; Gapstur S; Stevens VL; Tangen CM; Batra J; Clements J; Gronberg H; Schleutker J; Albanes D; Wolk A; West C; Mucci L; Cancel-Tassin G; Koutros S; Sorensen KD; Grindeda EM; Neal DE; Hamdy FC; Donovan JL; Travis RC; Hamilton RJ; Ingles SA; Rosenstein BS; Lu YJ; Giles GG; Kibel AS; Vega A; Kogevinas M; Penney KL; Park JY; Stanford JL; Cybulski C; Nordestgaard BG; Maier C; Kim J; John EM; Teixeira MR; Neuhausen SL; De Ruyck K; Razack A; Newcomb LF; Gamulin M; Kaneva R; Usmani N; Claessens F; Townsend PA; Gago-Dominguez M; Roobol MJ; Menegaux F; Khaw KT; Cannon-Albright L; Pandha H; Thibodeau SN

Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Law PJ
Timofeeva M
Fernandez-Rozadilla C
Timofeeva A
Broderick P
Studd J
Fernandez-Tajes J
Farrington S
Svinti V
Palles C
Orlando G
Sud A
Holroyd A
Penegar S
Theodoratou E
Vaughan-Shaw P
Campbell H
Zgaga L
Hayward C
Campbell A
Harris S
Deary IJ
Starr O
Gatcombe L
Pinna M
Briggs S
Martin L
Jaeger E
Sharma-Oates A
East J
Leedham S
Arnold R
Johnstone E
Wang H
Kerr D
Kerr R
Maughan T
Kaplan R
Al-Tassan N
Palin K
Hanninen UA
Cajuso T
Tanskanen T
Kondelin J
Kaasinen E
Sarin AP
Eriksson JG
Rissanen H
Knekt P
Pukkala E
Jousilahti P
Salomaa V
Ripatti S
Palotie A
Renkonen-Sinisalo L
Lepisto A
Bohm J
Mecklin JP
Buchanan DD
Win AK
Hopper J
Jenkins ME
Lindor NM
Newcomb PA
Gallinger S
Duggan D
Casey G
Hoffmann P
Nothen MM
Jockel KH
Easton DF
Pharoah PDP
Peto J
Canzian F
Swerdlow A
Eeles RA
Kote-Jarai Z
Muir K
Pashayan N
Harkin A
Allan K
McQueen J
Paul J
Iveson T
Saunders M
Butterbach K
Chang-Claude J
Hoffmeister M
Brenner H
Kirac I
Matosevic P
Hofer P
Brezina S
Gsur A
Cheadle JP
Aaltonen LA
Tomlinson I
Houlston RS
Dunlop MG
Henderson BE
Haiman CA
Schumacher FR
Al Olama AA
Benlloch S
Berndt SI
Conti DV
Wiklund F
Chanock S
Gapstur S
Stevens VL
Tangen CM
Batra J
Clements J
Gronberg H
Schleutker J
Albanes D
Wolk A
West C
Mucci L
Cancel-Tassin G
Koutros S
Sorensen KD
Grindeda EM
Neal DE
Hamdy FC
Donovan JL
Travis RC
Hamilton RJ
Ingles SA
Rosenstein BS
Lu YJ
Giles GG
Kibel AS
Vega A
Kogevinas M
Penney KL
Park JY
Stanford JL
Cybulski C
Nordestgaard BG
Maier C
Kim J
John EM
Teixeira MR
Neuhausen SL
De Ruyck K
Razack A
Newcomb LF
Gamulin M
Kaneva R
Usmani N
Claessens F
Townsend PA
Gago-Dominguez M
Roobol MJ
Menegaux F
Khaw KT
Cannon-Albright L
Pandha H
Thibodeau SN
Katso/Avaa
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NATURE PUBLISHING GROUP
doi:10.1038/s41467-019-09775-w
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042827199
Tiivistelmä
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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