Houlston Richard S, Webb Emily, Broderick Peter, Pittman Alan M, Di Bernardo Maria Chiara, Lubbe Steven, Chandler Ian, Vijayakrishnan Jayaram, Sullivan Kate, Penegar Steven, Carvajal-Carmona Luis, Howarth Kimberley, Jaeger Emma, Spain Sarah L, Walther Axel, Barclay Ella, Martin Lynn, Gorman Maggie, Domingo Enric, Teixeira Ana S, Kerr David, Cazier Jean-Baptiste, Niittymäki Iina, Tuupanen Sari, Karhu Auli, Aaltonen Lauri A, Tomlinson Ian P M, Farrington Susan M, Tenesa Albert, Prendergast James G D, Barnetson Rebecca A, Cetnarskyj Roseanne, Porteous Mary E, Pharoah Paul D P, Koessler Thibaud, Hampe Jochen, Buch Stephan, Schafmayer Clemens, Tepel Jurgen, Schreiber Stefan, Völzke Henry, Chang-Claude Jenny, Hoffmeister Michael, Brenner Hermann, Zanke Brent W, Montpetit Alexandre, Hudson Thomas J, Gallinger Steven, Campbell Harry, Dunlop Malcolm G
Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK.
Nat Genet. 2008 Dec;40(12):1426-35. doi: 10.1038/ng.262. Epub 2008 Nov 16.
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.
全基因组关联(GWA)研究已确定了多个位点,在这些位点上常见变异对患结直肠癌(CRC)的风险有适度影响。为了增强识别具有相似效应大小的其他位点的能力,我们对两项GWA研究进行了荟萃分析,这两项研究包括对13315名个体进行38710个常见标签单核苷酸多态性(SNP)的基因分型。我们在多达8个独立的病例对照系列中进行了重复测试,这些系列包括27418名受试者。我们在14q22.2(rs4444235,BMP4;P = 8.1×10⁻¹⁰)、16q22.1(rs9929218,CDH1;P = 1.2×10⁻⁸)、19q13.1(rs10411210,RHPN2;P = 4.6×10⁻⁹)和20p12.3(rs961253;P = 2.0×10⁻¹⁰)发现了四个先前未报告的CRC风险位点。这些发现强调了大样本系列对于发现和追踪有助于CRC病因的遗传变异的价值。