Cheng Iona, Plummer Sarah J, Jorgenson Eric, Liu Xin, Rybicki Benjamin A, Casey Graham, Witte John S
Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143-0794, USA.
Eur J Hum Genet. 2008 Apr;16(4):496-505. doi: 10.1038/sj.ejhg.5201959. Epub 2008 Jan 30.
Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. Multiple variants within three adjacent regions at 8q24 have recently been identified to impact the risk of prostate cancer. Yet, the role of these variants in more advanced disease has not been rigorously assessed. To examine the relationship between 8q24 variants and advanced disease, we tested 10 previously associated 8q24 variants in a case-control study of advanced prostate cancer (N=1012). Of these ten 8q24 variants, six were associated with the risk of advanced prostate cancer (P=0.001-0.038). Three of these variants (rs10090154-region 1, rs16901979-region 2, and rs6983267-region 3), each variant residing in one of the three previously reported 8q24 regions, could account for our 8q24 effects on advanced disease. A meta-analysis across 10 studies including our results of four 8q24 variants (rs1442295 and DG8S737-region 1, rs16901979-region 2, and rs6983267-region 3) and prostate cancer risk demonstrated strong associations across a wide array of study designs and populations. Our findings provide the first confirmation that the three 8q24 regions independently influence the risk of prostate cancer and, in particular, advanced disease.
有力证据表明8号染色体q24区域是前列腺癌易感位点。最近已确定8q24三个相邻区域内的多个变异会影响前列腺癌风险。然而，这些变异在更晚期疾病中的作用尚未得到严格评估。为了研究8q24变异与晚期疾病之间的关系，我们在一项晚期前列腺癌病例对照研究（N = 1012）中检测了10个先前相关的8q24变异。在这10个8q24变异中，有6个与晚期前列腺癌风险相关（P = 0.001 - 0.038）。其中三个变异（rs10090154 - 区域1、rs16901979 - 区域2和rs6983267 - 区域3），每个变异位于先前报道的8q24三个区域之一，可解释我们观察到的8q24对晚期疾病的影响。一项纳入10项研究的荟萃分析，包括我们关于4个8q24变异（rs1442295和DG8S737 - 区域1、rs16901979 - 区域2和rs6983267 - 区域3）与前列腺癌风险的研究结果，表明在广泛的研究设计和人群中存在强关联。我们的研究结果首次证实，8q24的这三个区域独立影响前列腺癌风险，尤其是晚期疾病风险。
