title: Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis.
abstract: To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5626 cases and 7817 controls of European descent. We conducted replication of top ranked single nucleotide polymorphisms (SNPs) in additional series totalling 14 037 cases and 15 937 controls, identifying a new CRC risk locus at 10q24.2 [rs1035209; odds ratio (OR) = 1.13, P = 4.54 × 10(-11)]. We also performed meta-analysis of our studies, with previously published data, of several recently purported CRC risk loci. We failed to find convincing evidence for a previously reported genome-wide association at rs11903757 (2q32.3). Of the three additional loci for which evidence of an association in Europeans has been previously described we failed to show an association between rs59336 (12q24.21) and CRC risk. However, for the other two SNPs, our analyses demonstrated new, formally significant associations with CRC. These are rs3217810 intronic in CCND2 (12p13.32; OR = 1.19, P = 2.16 × 10(-10)) and rs10911251 near LAMC1 (1q25.3; OR = 1.09, P = 1.75 × 10(-8)). Additionally, we found some evidence to support a relationship between, rs647161, rs2423297 and rs10774214 and CRC risk originally identified in East Asians in our European datasets. Our findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC.
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Whiffin
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Fay J
authors.initials: FJ
authors.lastname: Hosking
authors.affiliation: Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Farrington
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Palles
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Dobbins
authors.affiliation: Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Lina
authors.initials: L
authors.lastname: Zgaga
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Lloyd
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Kinnersley
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: Maggie
authors.initials: M
authors.lastname: Gorman
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Roslin EH25 9RG, UK.
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: Ella
authors.initials: E
authors.lastname: Barclay
authors.affiliation: Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: Martin
authors.affiliation: Cancer and Population Studies Group, Queensland Institute of Medical Research, Queensland, Australia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.affiliation: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Victoria, Australia.
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
authors.affiliation: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Victoria, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Hopper
authors.affiliation: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkins
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Conti
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Schumacher
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Lindblom
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK richard.houlston@icr.ac.uk iant@well.ox.ac.uk malcolm.dunlop@igmm.ed.ac.uk.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Roslin EH25 9RG, UK richard.houlston@icr.ac.uk iant@well.ox.ac.uk malcolm.dunlop@igmm.ed.ac.uk.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Tomlinson
authors.affiliation: Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK richard.houlston@icr.ac.uk iant@well.ox.ac.uk malcolm.dunlop@igmm.ed.ac.uk.
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Dunlop
mesh_terms: D044466:Asian People / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D044465:White People / Q000235:genetics
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