학술논문
Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.
Document Type
Article
Author
Tenesa, Albert; Farrington, Susan M.; Prendergast, James G. D.; Porteous, Mary E.; Walker, Marion; Haq, Naila; Barnetson, Rebecca A.; Theodoratou, Evropi; Cetnarskyj, Roseanne; Cartwright, Nicola; Semple, Colin; Clark, Andrew J.; Reid, Fiona J. L.; Smith, Lorna A.; Kavoussanakis, Kostas; Koessler, Thibaud; Pharoah, Paul D. P.; Buch, Stephan; Schafmayer, Clemens; Tepel, Jürgen
Source
Subject
*COLON cancer
*GENOMES
*ETIOLOGY of cancer
*ETIOLOGY of diseases
*BIOLOGICAL variation
*GENETIC research
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Language
ISSN
1061-4036
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 × 10−10), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 × 10−26) and 18q21 (rs4939827; OR = 1.2; P = 7.8 × 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. [ABSTRACT FROM AUTHOR]