Di Bernardo Maria Chiara, Crowther-Swanepoel Dalemari, Broderick Peter, Webb Emily, Sellick Gabrielle, Wild Ruth, Sullivan Kate, Vijayakrishnan Jayaram, Wang Yufei, Pittman Alan M, Sunter Nicola J, Hall Andrew G, Dyer Martin J S, Matutes Estella, Dearden Claire, Mainou-Fowler Tryfonia, Jackson Graham H, Summerfield Geoffrey, Harris Robert J, Pettitt Andrew R, Hillmen Peter, Allsup David J, Bailey James R, Pratt Guy, Pepper Chris, Fegan Chris, Allan James M, Catovsky Daniel, Houlston Richard S
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Nat Genet. 2008 Oct;40(10):1204-10. doi: 10.1038/ng.219. Epub 2008 Aug 31.
We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 x 10(-10)), 2q37.1 (rs13397985, SP140; P = 5.40 x 10(-10)), 6p25.3 (rs872071, IRF4; P = 1.91 x 10(-20)), 11q24.1 (rs735665; P = 3.78 x 10(-12)), 15q23 (rs7176508; P = 4.54 x 10(-12)) and 19q13.32 (rs11083846, PRKD2; P = 3.96 x 10(-9)). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL.
我们针对慢性淋巴细胞白血病（CLL）的299,983个标签单核苷酸多态性（SNP）进行了全基因组关联研究，并在另外两个系列中进行了验证，这两个系列共有1,529例病例和3,115例对照。我们在2q13（rs17483466；P = 2.36 x 10(-10)）、2q37.1（rs13397985，SP140；P = 5.40 x 10(-10)）、6p25.3（rs872071，IRF4；P = 1.91 x 10(-20)）、11q24.1（rs735665；P = 3.78 x 10(-12)）、15q23（rs7176508；P = 4.54 x 10(-12)）和19q13.32（rs11083846，PRKD2；P = 3.96 x 10(-9)）处鉴定出六个先前未报道的CLL风险位点。这些数据首次证明了对血液系统恶性肿瘤存在常见的低 penetrance 易感性，并为CLL的疾病病因提供了新的见解。
