1. ¹Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143-0794, USA
2. ²Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA
3. ³Mary Ann and J Milburn Smith Child Health Research Program, Department of Pediatrics, Northwestern University, Feinberg School of Medicine and Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL 60614, USA
4. ⁴Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, MI 48202, USA
5. ⁵Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA

Correspondence: Dr JS Witte, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143-0794, USA. Tel: +1 415 502 6882; Fax: +1 415 476 1356; E-mail: wittej@humgen.ucsf.edu

Received 29 August 2007; Revised 10 October 2007; Accepted 19 October 2007; Published online 30 January 2008.

Abstract

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.