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Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.


ABSTRACT: In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.

SUBMITTER: Tenesa A 

PROVIDER: S-EPMC2778004 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.

Tenesa Albert A   Farrington Susan M SM   Prendergast James G D JG   Porteous Mary E ME   Walker Marion M   Haq Naila N   Barnetson Rebecca A RA   Theodoratou Evropi E   Cetnarskyj Roseanne R   Cartwright Nicola N   Semple Colin C   Clark Andrew J AJ   Reid Fiona J L FJ   Smith Lorna A LA   Kavoussanakis Kostas K   Koessler Thibaud T   Pharoah Paul D P PD   Buch Stephan S   Schafmayer Clemens C   Tepel Jürgen J   Schreiber Stefan S   Völzke Henry H   Schmidt Carsten O CO   Hampe Jochen J   Chang-Claude Jenny J   Hoffmeister Michael M   Brenner Hermann H   Wilkening Stefan S   Canzian Federico F   Capella Gabriel G   Moreno Victor V   Deary Ian J IJ   Starr John M JM   Tomlinson Ian P M IP   Kemp Zoe Z   Howarth Kimberley K   Carvajal-Carmona Luis L   Webb Emily E   Broderick Peter P   Vijayakrishnan Jayaram J   Houlston Richard S RS   Rennert Gad G   Ballinger Dennis D   Rozek Laura L   Gruber Stephen B SB   Matsuda Koichi K   Kidokoro Tomohide T   Nakamura Yusuke Y   Zanke Brent W BW   Greenwood Celia M T CM   Rangrej Jagadish J   Kustra Rafal R   Montpetit Alexandre A   Hudson Thomas J TJ   Gallinger Steven S   Campbell Harry H   Dunlop Malcolm G MG  

Nature genetics 20080330 5


In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842  ...[more]

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