The Common Variant rs1447295 on Chromosome 8q24 and Prostate Cancer Risk: Results from an Australian Population-Based Case-Control Study

Abstract

A recent study from deCode reported an association between common variants in the region 8q24 and prostate cancer risk. The strongest association was found with the single nucleotide polymorphism rs1447295. We genotyped 821 prostate cancer cases and 732 population controls for rs1447295 to test the association between this common variant and prostate cancer risk, and examine whether this association depends on Gleason score. Our case-control study confirmed the association between rs1447295 and prostate cancer risk (P = 0.0005). The odds ratio (OR) for prostate cancer was 1.52 [95% confidence interval (CI), 1.20-1.93] for carriers of any A allele compared with noncarriers. The OR for Gleason score 5 to 6 prostate cancer (1.48; 95% CI, 1.13-1.95) was similar to the OR for Gleason score 7 to 10 prostate cancer (1.58; 95% CI, 1.18-2.11, P for heterogeneity = 0.7). We conclude that the A allele of rs1447295 is associated with a higher risk of prostate cancer regardless of tumor aggressiveness, suggesting that such a variant, or a variant in linkage disequilibrium with it, plays a role early in prostate carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2007;16(3):610 -2)

Confirmation study of prostate cancer risk variants at 8q24 in African Americans identifies a novel risk locus

“…Further genotyping within this region and functional analyses are underway. We also note that among our African American subjects, we did not observe an association to the 128.6 Mb region, which maps to the distal 8q24.21 locus originally reported by Amundadottir et al 2006; although the region has been shown by others to influence risk for prostate cancer (Gudmundsson et al 2007;Schumacher et al 2007;Severi et al 2007;Suuriniemi et al 2007;Wang et al 2007;Yeager et al 2007). …”

“…Ignoring differences in local ancestry across African American subjects may account for the differences observed in previous studies. Yet, strong and replicable association with both DG8S737 and rs1447295 are seen among cohorts of European ancestry (Schumacher et al 2007;Severi et al 2007;Suuriniemi et al 2007;Wang et al 2007). In a study of 1121 European descent familial and sporadic PCa cases, Wang et al (2007) reported significant association with both familial (P = 0.0004) and aggressive prostate cancer (P = 0.0005) and SNP rs1447295 (Wang et al 2007).…”

“…Furthermore, results of an independent genome-wide scan in ∼1200 prostate cancer cases and ∼1200 matched controls were reported, with markers within 8q24 showing the strongest evidence of association (Yeager et al 2007). Recently, there have been four independent confirmation reports replicating the association of prostate cancer with variants mapping within the 8q24 region of the genome (Schumacher et al 2007;Severi et al 2007;Suuriniemi et al 2007;Wang et al 2007). These associations along with the fact that the chromosome region 8q24 is amplified in most prostate tumors and has been associated with aggressive disease and poor prognosis (Jenkins et al 1997;El Gedaily et al 2001;Tan et al 2003;Liu et al 2006;Sun et al 2007;Tan and Chow 2007) make it an interesting region to explore prostate cancer risk.…”

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

“…These four variants were chosen because they have the most data available for each of the three 8q24 regions. We also conducted a metaanalysis for advanced prostate cancer from available data for the rs1447295 1,6,7,9 and DG8S737 variants, 1,5,8,9 including our results. Allele-specific ORs were abstracted from published studies.…”

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

“…[49][50][51] This 7.5-Mb locus overlaps with the 8q24 region, which has been reported in linkage and GWASs of PrCa 17,23,24,29,32 and has been replicated in many studied populations. 22,25,26,[52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] The prostate stem cell antigen maps to this region 69 as does the oncogene MYC. The region has been extensively studied and is relatively gene-poor.…”