Top image: Schumacher et al. replicated the overall association between an 8q24 single nucleotide polymorphism (rs1447295) and prostate cancer risk previously identified by two independent studies in a large pooled analysis from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3) using 6,637 prostate cancer cases and 7,361 matched controls. The odds ratios and 99% CI for prostate cancer are presented among Caucasians in the middle panel and the corresponding -Log p-values from the two degrees-of-freedom LRT are shown in the right panel. The overall prostate cancer risk in Caucasians was 1.34 (99%CI: 1.19, 1.50) in men with one copy of the minor allele (A) and 1.86 (99%CI: 1.30, 2.67) in men with two copies of the minor allele compared with wild-type homozygotes (LRT p=1.23 x 10^-13). The authors found no significant association between this polymorphism and breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls in BPC3. Our large sample size leaves little room for the possibility of a false-positive result between this locus and prostate cancer risk.

Bottom image: Wang et al. It is well accepted that genetics plays an important role in prostate cancer. However, due to the complex nature of this disease, the identification of candidate susceptibility genes has been enormously challenging. Recently, using both linkage and association-based analyses, Amundadottir et al. identified a region on chromosome 8q24 showing suggestive linkage to prostate cancer and further identified two common variants (rs1447295/DG8S737) associated with prostate cancer risk. In a study comprising 1,121 men with prostate cancer (435 men with familial prostate cancer, 491 men with sporadic prostate cancer, and 195 men with aggressive prostate cancer) and 545 population-based controls, Wang et al. present data replicating these findings reported by Amundadottir et al. Given the historical difficulty in replicating both linkage and gene association studies in prostate cancer, these confirmatory findings provide important clues towards the identification of candidate genetic susceptibility factors. The functional significance of the two polymorphic variants, however, remains unclear and is the subject of ongoing research. The figure (generated from UCSC genome browser) illustrates the location of the two variants (DG8S737 and rs1447295) along with the position of known genes, predicted genes, mRNAs, and a linkage disequilibrium map in the region of interest covering ~500Kb.

For details, see the articles by Schumacher et al. on page 2951 and Wang et al. on page 2944, as well as a commentary on these findings by Dr. Elizabeth A. Platz on page 2905 of this issue.


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