Genome-wide Association Scan Identifies a Colorectal Cancer Susceptibility Locus on 11q23 and Replicates Risk Loci at 8q24 and 18q21

Nat Genet. 2008 May;40(5):631-7. doi: 10.1038/ng.133. Epub 2008 Mar 30.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chromosomes, Human, Pair 11 / genetics*
  • Chromosomes, Human, Pair 18 / genetics*
  • Chromosomes, Human, Pair 8 / genetics*
  • Colorectal Neoplasms / genetics*
  • Female
  • Genetic Linkage*
  • Genetic Predisposition to Disease*
  • Genome, Human
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk