A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall; P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.
Tomlinson
Ian P M
IP
Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK. ian.tomlinson@cancer.org.uk
Webb
Emily
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Carvajal-Carmona
Luis
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Broderick
Peter
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Howarth
Kimberley
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Pittman
Alan M
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Spain
Sarah
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Lubbe
Steven
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Walther
Axel
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Sullivan
Kate
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Jaeger
Emma
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Fielding
Sarah
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Rowan
Andrew
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Vijayakrishnan
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Domingo
Enric
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Chandler
Ian
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Kemp
Zoe
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James G D
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Wood
Wendy
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Martin
Lynn
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Gorman
Maggie
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Huw
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Peto
Julian
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Bishop
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Gray
Richard
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Maher
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Lucassen
Anneke
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Kerr
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Evans
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Schafmayer
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Buch
Stephan
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Völzke
Henry
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Hampe
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Schreiber
Stefan
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John
Ulrich
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Koessler
Thibaud
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Pharoah
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van Wezel
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Severi
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Castellví-Bel
Sergi
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Ruiz-Ponte
Clara
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Angel
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Castells
Antoni
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Försti
Asta
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Hemminki
Kari
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Vodicka
Pavel
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Naccarati
Alessio
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Lipton
Lara
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Judy W C
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Cheng
K K
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Sham
Pak C
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Luk
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de la Hoya
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Iina
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Sari
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Karhu
Auli
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D000328:Adult; D000368:Aged; D000483:Alleles; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
D039621:Eukaryotic Initiation Factor-3