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

Journal article

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.

Authors: Tenesa, A; Farrington, S; Prendergast, J; Porteous, M; Walker, M

• Journal: Nature genetics
• Volume: 40
• Issue: 5
• Pages: 631-637
• Publication date: 2008-05-01
• DOI: 10.1038/ng.133
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Chromosomes, Human, Pair 8; Chromosomes, Human, Pair 18; Aged; Genetic Linkage; Adult; Colorectal Neoplasms; Humans; Chromosomes, Human, Pair 11; Male; Genome, Human; Polymorphism, Single Nucleotide; Female; Genetic Predisposition to Disease; Middle Aged; Risk