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PMID: 22634755 Published · epublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.

Nature genetics ·Vol. 44 ·No. 7 ·2012-05-27 ·Pages 770-6

Dunlop MG, Dobbins SE, Farrington SM, Jones AM, Palles C, Whiffin N, Tenesa A, Spain S, Broderick P, Ooi LY, Domingo E, Smillie C, Henrion M, Frampton M, Martin L, Grimes G, Gorman M, Semple C, Ma YP, Barclay E, Prendergast J, Cazier JB, Olver B, Penegar S, Lubbe S, Chander I, Carvajal-Carmona LG, Ballereau S, Lloyd A, Vijayakrishnan J, Zgaga L, Rudan I, Theodoratou E, Colorectal Tumour Gene Identification CORGI Consortium, Starr JM, Deary I, Kirac I, Kovacević D, Aaltonen LA, Renkonen-Sinisalo L, Mecklin JP, Matsuda K, Nakamura Y, Okada Y, Gallinger S, Duggan DJ, Conti D, Newcomb P, Hopper J, Jenkins MA, Schumacher F, Casey G, Easton D, Shah M, Pharoah P, Lindblom A, Liu T, Swedish Low-Risk Colorectal Cancer Study Group, Smith CG, West H, Cheadle JP, COIN Collaborative Group, Midgley R, Kerr DJ, Campbell H, Tomlinson IP, Houlston RS

Abstract

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

MeSH Terms
Case-Control Studies Colorectal Neoplasms/genetics Cyclin-Dependent Kinase Inhibitor p21/genetics DNA Polymerase III/genetics Genetic Loci Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study/methods Humans Membrane Proteins/genetics
Chemicals
CDKN1A protein, human Cyclin-Dependent Kinase Inhibitor p21 Membrane Proteins SHROOM2 protein, human POLD3 protein, human DNA Polymerase III
Authors & Affiliations
67 authors, click to expand affiliations / ORCID
Dunlop Malcolm G
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK. [email protected]
Dobbins Sara E
Farrington Susan Mary
Jones Angela M
Palles Claire
Whiffin Nicola
Tenesa Albert
Spain Sarah
Broderick Peter
Ooi Li-Yin
Domingo Enric
Smillie Claire
Henrion Marc
Frampton Matthew
Martin Lynn
Grimes Graeme
Gorman Maggie
Semple Colin
Ma Yusanne P
Barclay Ella
Prendergast James
Cazier Jean-Baptiste
Olver Bianca
Penegar Steven
Lubbe Steven
Chander Ian
Carvajal-Carmona Luis G
Ballereau Stephane
Lloyd Amy
Vijayakrishnan Jayaram
Zgaga Lina
Rudan Igor
Theodoratou Evropi
Colorectal Tumour Gene Identification (CORGI) Consortium
Starr John M
Deary Ian
Kirac Iva
Kovacević Dujo
Aaltonen Lauri A
Renkonen-Sinisalo Laura
Mecklin Jukka-Pekka
Matsuda Koichi
Nakamura Yusuke
Okada Yukinori
Gallinger Steven
Duggan David J
Conti David
Newcomb Polly
Hopper John
Jenkins Mark A
Schumacher Fredrick
Casey Graham
Easton Douglas
Shah Mitul
Pharoah Paul
Lindblom Annika
Liu Tao
Swedish Low-Risk Colorectal Cancer Study Group
Smith Christopher G
West Hannah
Cheadle Jeremy P
COIN Collaborative Group
Midgley Rachel
Kerr David J
Campbell Harry
Tomlinson Ian P
Houlston Richard S
Investigators
306 investigators, click to expand
MacDonald Graham
Samuel Leslie M
Ahmad Athar
Corrie Philippa
Jodrell Duncan
Palmer Cheryl
Wilson Charles
O'Hagan Julie
Smith David
McDermott Ray
Walshe Janice
Cassidy James
McDonald Alec
Mohammed Nazia
White Jeff
Yosef Hosney
Breathnach Oscar
Grogan Liam
Thomas Robert
Eatock Martin
Henry Paul
Houston Russell
Johnston Patrick
Wilson Richard
Geh Ian
Danwata Falalu
Hindley Andrew
Susnerwala Shabbir
Bradley Chris
Conn Andrew
Raine Anne
Twelves Chris
Falk Stephen
Hopkins Kirstin
Tahir Saad
Dhadda Amandeep
Maraveyas Anthony
Sgouros Joseph
Teo Mark
Ahmad Rizvana
Cleator Susan
Creak Antonia
Lowdell Charles
Riddle Philippa
Benstead Kim
Farrugia David
Reed Nicholas
Shepherd Stephen
Levine Edward
Mullamitha Saifee
Saunders Mark
Valle Juan
Wilson Gregory
Jones Adam
Weaver Andrew
Clark Peter I
Haylock Brain
Iqbal Mussawar I
Myint Arthur S
Smith David
Beesley Sharon
Sevitt Timothy
Nicoll Jonathan
Daniel Francis
Ford Victoria
Talbot Toby
Butt Mohammad
Hamid Abdel
Mack Paul
Roy Raj
Osborne Richard
McKinna Fiona
Alsab Heidar
Basu Devyanee
Murray Phillip
Sizer Bruce
Azam Faisal A
Neupane Rekha
Waterston Ashita
Glaholm John
Blesing Claire
Lowndes Sarah
Medisetti Aruna
Gaya Andrew
Leslie Martin
Maisey Nicholas
Ross Paul
Dunn Grainne
Al-Salihi Omar
Wasan S
Palmer Cheryl
Tan Li Tee
Dent Jo
Hofmann Uschi
Joffe Johnathan K
Sherwin Elizabeth
Soomal Rabinder
Chakrabarti Amitabha
Joseph Shibu
Van der Voet Johannes
Wadd Nicholas J
Wilson David
Anjarwalia Salim
Hall Julia
Hughes Rob
Polychronis Andrew
Scarffe John H
Hill Mark
James Rodger D
Shah Riyaz
Summers Jeffrey
Hartley Andrew
Carney Desmond
McCaffrey John
Bystricky Brano
O'Reilly Seamus
Gupta Rajnish
Al-Mishlab Talib
Gidden Fiona
O'Hara Richard
Stewart Jill
Ashford Richard
Glynne-Jones Robert
Harrison Mark
Mawdsley Suzannah
Barlow Hilary
Tighe Mary
Walther Julie
Neal Janet
Rees Charlotte
Bridgewater John
Karp Stephen
McGovern Ursula
Atherton Philip J
El-deeb Hany
Macmillan Craig
Patel Kinnari
Bessell Eric Michael
Dickinson Peter D
Potter Vanessa
Jephcott Catherine
McAdam Karen
Wrigley Jessica
Osborne Richard
Muthuramalingam Sethupathi
O'Callaghan Anne
Bridgewater John
Melcher Lucinda
Braconi Chiara
Geh Ju Ian
Palmer Dan
Narayana Priya
Steven Neil
Gaya Andres
Maisey Nicholas
Rudman Sarah
Chakraborti Prabir
Kelly Kay
Macgregor Carol
Whillis David
Freebairn Alice
Gildersleve James
Sharif Sahid
Astras George
Hickish Tamas
Beech Darren
Ellis Richard
Kulkarni Rajendra
Shankland K
Begent Richard
Mayer Astrid
Meyer Timothy
Strauss Sandra
Hall Viriginia
Raj Sanjay
Chau Ian
Cunningham David
Birtle Alison
Biswas Ashoke
Susnerwala Shabbir
Wise Marcus
Cummins Sebastian
Essapen Sharadah
Middleton Gary
Topham Claire
Langley Ruth
McKinna Fiona
Webb Andrew
Wilkins Marie
Iveson Timothy John
Dhadda Amandeep
Hamid Abdel
Askill Colin
Wagstaff John
Azzabi Ashraf
Bateman Adrian
Prejbisz Jan
Tsang David
Ali Nasim
Jones Amanda
O'Neill Paul
Cottrill Christopher
Propper David
Lofts Fiona Jane
Kennedy James
Anthoney David A
Cooper Rachel
Crellin Adrian
Melcher Alan
Seymour Matthew
Baughan Christopher
Alexander Emma
Cleator Susan
Crown John
Fennelly David
Adab Fawzi
Giridharan Selvaraj
Pedley Ian
Wright Kathryn
Bliss Peter
Cogill Geoffrey
Lo Nangi
Toy Elizabeth
Bridgewater John
Hochhauser Daniel
Ledermann Jonathan
Brewster Alison
Maughan Timothy
Mort Diana
Mukherjee Somnath
Dobrowsky Werner
Calvert Paula
Leonard Gregory
Ahmad Rizvana
Ford Hugo
Moody Anne Margeret
Goriah Sonia
Wilkins Margeret
Clive Sally
Dawson Lesley
McLean Catriona
Phillips Hamish Andrew
Gopi Kakumudi
Tomlinson Marjorie
Clenton Susan
Furniss Debra
Hornbuckle Joanne
Pledge Simon
Wadsley Jonathan
Abbas Mohammed
Marshall Ernest
Harper-Wynne Catherine
Barnes Anne
Kumar Satish
Vigneswaran Vallipuram
Farrugia David
Webb Andrew
Gollins Simon
Falk Stephen
Genton M
Sparrow Geoff
Bale Catherine
Fuller C
Mullard Anna
Stuart Nicholas
Williams Rachel
Keane Maccon
Maughan Tim
Seymour Matthew
Wilson Richard
Wasan Harpreet
Adams Richard
Madi Ayman
Cassidy James
Kennedy James
Hodgkinson Elizabeth
Rogers Penny
Pope Malcolm
Kaplan Rick
Meade Angela
Parmar Mahesh
Kenny Sarah
Fisher David
Harper Lynda
Mitchell Jena
Nichols Laura
Sydes Benjamin
Clement Louise
Kay Edward
Courtney Cheryl
Gallagher Madalena
Murphy Claire
Thompson Lindsay
Beall Sarah
Hassan Sharma
Gracie Richard
Griffiths Gareth
Mason Malcolm
Parker Chris
Rudd Robin
Johnson Patrick
Whelan Jeremy
Northover John
Brown Julia
Aapro Matti
Stout Ronald
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.2293
Email
[email protected]
Published
2012-05-27
Epub
2012-00-27
Pages
770-6
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC4747430
Subset
IM
Grants
Worldwide Cancer Research · 05-0001 · United Kingdom
NCI NIH HHS · U01 CA074799 · United States
Cancer Research UK · 12076 · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
Medical Research Council · MC_U122861325 · United Kingdom
Cancer Research UK · C10195/A12996 · United Kingdom
Cancer Research UK · 13154 · United Kingdom
NCI NIH HHS · U01 CA097735 · United States
NCI NIH HHS · CA-95-011 · United States
NCI NIH HHS · U01 CA074783 · United States
Cancer Research UK · 10589 · United Kingdom
Cancer Research UK · C1298/A8362 · United Kingdom
Cancer Research UK · 10124 · United Kingdom
Medical Research Council · MC_U127527198 · United Kingdom
NCI NIH HHS · U01CA122839 · United States
Cancer Research UK · C490/A10124 · United Kingdom
NCI NIH HHS · U01 CA074794 · United States
Cancer Research UK · C31250/A10107 · United Kingdom
Wellcome Trust · 090532 · United Kingdom
Wellcome Trust · 090532/Z/09/Z · United Kingdom
Cancer Research UK · C10314/A4886 · United Kingdom
Cancer Research UK · C348/A12076 · United Kingdom
Medical Research Council · G1002033 · United Kingdom
NCI NIH HHS · U01 CA122839 · United States
Wellcome Trust · 076113/C/04/Z · United Kingdom
Corrections
CommentIn
PMID: 23073136
External Links
PubMed source DOI: 10.1038/ng.2293 PMC Full Text View journal details
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