8q24 and prostate cancer: association with advanced disease and meta-analysis

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.

Figure 1

Chromosome 8 and 8q24 locus. Vertical black lines depict the ten 8q24 variants genotyped in our case–control study of advanced prostate cancer. Horizontal black bars indicate region 1 (126.54–128.62 Mb), region 2 (128.14–128.28 Mb), and region 3 (128.47–128.54 Mb) of the 8q24 locus.

Figure 2

a Meta-analysis of 8q24 variants and prostate cancer. *Allele-specific odds ratio estimated by reported allele frequencies and case–control study numbers. ^†Wang et al sporadic prostate cancer results. (a) rs1447295-region 1 (A allele vs C allele) and prostate cancer across 24 study panels from nine studies. (b) DG8S737-region 1 (−8 allele vs all other alleles) and prostate cancer across 13 study panels from five studies. (c) rs16901979-region 2 (A allele vs C allele) and prostate cancer across 12 study panels from three studies. (d) rs6983267-region 3 (G allele vs T allele) and prostate cancer across 12 study panels from three studies.

Figure 2

a Meta-analysis of 8q24 variants and prostate cancer. *Allele-specific odds ratio estimated by reported allele frequencies and case–control study numbers. ^†Wang et al sporadic prostate cancer results. (a) rs1447295-region 1 (A allele vs C allele) and prostate cancer across 24 study panels from nine studies. (b) DG8S737-region 1 (−8 allele vs all other alleles) and prostate cancer across 13 study panels from five studies. (c) rs16901979-region 2 (A allele vs C allele) and prostate cancer across 12 study panels from three studies. (d) rs6983267-region 3 (G allele vs T allele) and prostate cancer across 12 study panels from three studies.

Figure 2

a Meta-analysis of 8q24 variants and prostate cancer. *Allele-specific odds ratio estimated by reported allele frequencies and case–control study numbers. ^†Wang et al sporadic prostate cancer results. (a) rs1447295-region 1 (A allele vs C allele) and prostate cancer across 24 study panels from nine studies. (b) DG8S737-region 1 (−8 allele vs all other alleles) and prostate cancer across 13 study panels from five studies. (c) rs16901979-region 2 (A allele vs C allele) and prostate cancer across 12 study panels from three studies. (d) rs6983267-region 3 (G allele vs T allele) and prostate cancer across 12 study panels from three studies.

Figure 2

a Meta-analysis of 8q24 variants and prostate cancer. *Allele-specific odds ratio estimated by reported allele frequencies and case–control study numbers. ^†Wang et al sporadic prostate cancer results. (a) rs1447295-region 1 (A allele vs C allele) and prostate cancer across 24 study panels from nine studies. (b) DG8S737-region 1 (−8 allele vs all other alleles) and prostate cancer across 13 study panels from five studies. (c) rs16901979-region 2 (A allele vs C allele) and prostate cancer across 12 study panels from three studies. (d) rs6983267-region 3 (G allele vs T allele) and prostate cancer across 12 study panels from three studies.