Journal
EUROPEAN JOURNAL OF HUMAN GENETICS
Volume 16, Issue 4, Pages 496-505Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.ejhg.5201959
Keywords
8q24; prostate cancer; SNPs; genetic association study
Funding
- NCI NIH HHS [T32 CA112355, R01 CA088164, CA94211, CA98683, CA88164, R01 CA098683, R25T CA112355, R25 CA112355, R01 CA094211] Funding Source: Medline
- NIEHS NIH HHS [R01 ES011126-06A2, R01 ES011126, R01 ES011126-05] Funding Source: Medline
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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.
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