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In 2006 about 234,460 men in the U.S. will be diagnosed with prostate cancer and nearly 27,500 deaths will be attributed to the disease. Family-based linkage studies, association studies, and studies of prostate tumors have highlighted human chromosome 8q as a genomic region of interest for susceptibility loci. Recently, a locus at 8q24, characterized by both a single nucleotide polymorphism (SNP) (rs1447295) and a microsatellite marker (DG8S737), was shown to be associated with prostate cancer risk in Icelandic, Swedish, and U.S. populations (Nature Genetics: 38, 652-658, 2006). While the data were provocative, the U.S. sample was not population-based, which precludes assessment of the potential contribution of this locus to prostate cancer incidence in the U.S.

We have analyzed both markers in a population-based, case-control study of Caucasian middle-aged men from King County, Washington (597 cases and 548 controls). We were particularly interested in evaluating the risk of prostate cancer associated with these genetic variants according to the clinical features of the disease and how much these variants may contribute to prostate cancer incidence in the general U.S. population.

Overall, we found a significant positive association between the A allele of the SNP rs1447295 and prostate cancer risk [odds ratio (OR) = 1.4, 95% confidence interval (CI) 1.1-2.0], but no significant association with the microsatellite DG8S737. However, significant associations were observed for both markers in men with more aggressive tumors defined by a high Gleason score (7=4+3 or 8-10). After adjusting for age, first-degree family history of prostate cancer, and prostate cancer screening, the ORs were 1.4 (95% CI 1.1-1.8) for the A allele of the SNP and 1.9 (95% CI 1.2-2.8) for the -10 allele of the microsatellite, respectively. No associations were observed in men with lower Gleason scores (2-6 or 7=3+4).

These data suggest that the locus on chromosome 8q24 contributes most importantly to more aggressive forms of prostate cancer among Caucasian men from the general population. Additional studies are needed to define the specific genetic variant underlying risk associated with this genomic region to prostate cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA