TY - JOUR
T1 - A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21
AU - Tomlinson, Ian
AU - Webb, Emily
AU - Carvajal-Carmona, Luis
AU - Broderick, Peter
AU - Kemp, Zoe
AU - Spain, Sarah
AU - Penegar, Steven
AU - Chandler, Ian
AU - Gorman, Maggie
AU - Wood, Wendy
AU - Barclay, Ella
AU - Lubbe, Steven
AU - Martin, Lynn
AU - Sellick, Gabrielle
AU - Jaeger, Emma
AU - Hubner, Richard
AU - Wild, Ruth
AU - Rowan, Andrew
AU - Fielding, Sarah
AU - Howarth, Kimberley
AU - Silver, Andrew
AU - Atkin, Wendy
AU - Muir, Kenneth
AU - Logan, Richard
AU - Kerr, David
AU - Johnstone, Elaine
AU - Sieber, Oliver
AU - Gray, Richard
AU - Thomas, Huw
AU - Peto, Julian
AU - Cazier, Jean Baptiste
AU - Houlston, Richard
N1 - Funding Information:
We thank all the affected and control individuals for their participation, and we thank C. Thirlwell, K. Monahan, A. Walther, J. Harvey, H. Schaschl, C. Cummings, E Volikos, G. Clark and colleagues. This work was principally supported by a grant from Cancer Research UK. Additional grant support was provided by CORE, the European Union (CCPRB LSHC-CT-2004-503465), the Bobby Moore Fund and the Thomas Falknor Fund. P.B. and G.S. are funded by Leukaemia Research. R. Hubner is in receipt of a Clinical Training Fellowship from Cancer Research UK.
PY - 2007/8
Y1 - 2007/8
N2 - Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 × 10-7, allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 × 10-14 (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34; P = 6.89 × 10-5). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.
AB - Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 × 10-7, allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 × 10-14 (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34; P = 6.89 × 10-5). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.
UR - http://www.scopus.com/inward/record.url?scp=34547498546&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547498546&partnerID=8YFLogxK
U2 - 10.1038/ng2085
DO - 10.1038/ng2085
M3 - Article
C2 - 17618284
AN - SCOPUS:34547498546
SN - 1061-4036
VL - 39
SP - 984
EP - 988
JO - Nature Genetics
JF - Nature Genetics
IS - 8
ER -
