4.8 Article

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24

Journal

NATURE GENETICS
Volume 39, Issue 8, Pages 989-994

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ng2089

Keywords

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Funding

  1. MRC [MC_U127527198] Funding Source: UKRI
  2. Chief Scientist Office [CZB/4/449] Funding Source: researchfish
  3. Medical Research Council [MC_U127527198] Funding Source: researchfish
  4. Medical Research Council [MC_U127527198] Funding Source: Medline
  5. NCI NIH HHS [RFA CA-95-011, U01 CA076783, U01 CA074794, U01 CA074783] Funding Source: Medline
  6. Chief Scientist Office [CZB/4/449] Funding Source: Medline

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Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 = 10-4). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer(1-3).

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