Of the 776 samples genotyped, a total of 482 cases and 261 controls were eligible for inclusion in the analyses. 33 samples (4.4%) were excluded because they failed one of the standard data quality checks described in previous reports (Freedman et al. 2006
; Reich et al. 2005
). Briefly, samples were removed if they had a much lower genotyping completeness than other samples used in the analysis based on an empirical inspection of the distribution, if they were duplicates or first degree relatives of other samples in the analysis, if they had greater than about 85% European origin from our analysis, or if they had one parent of entirely European origin. The mean estimated individual admixture proportions after removal of the outlier samples were 20% European and 80% African. Patient characteristics overall and by study site are described in . Equal numbers of cases were derived from each source, and a greater proportion of the controls came from HU. Cases from HU were significantly older than cases from HFHS, and controls from HU were significantly younger than controls from HFHS. Median PSA in the HFHS cases was significantly lower than the median PSA in the HU cases, and there was no difference between the two sites with respect to median PSA in the controls.
Participant characteristics, overall and by study site
The age-adjusted genomewide z-scores for the case-only analyses are presented in , and information about markers at local peaks with |Z| >3.0 is summarized in . In general, results from the case-control analyses did not differ greatly from those obtained using the more powerful case-only approach, therefore only case-only results are presented unless discrepancies in inferences from the two methods occurred. The greatest observed increase in ancestry occurred at marker rs2141360 on chromosome 7 (), where excess European ancestry was observed (case-only p=0.0000036). The greatest observed increase in African ancestry across the genome occurred at rs7729084 on Chromosome 5q35 in the case-only analysis (p=0.0016, ), and at marker rs12474977 in the case-control analysis (p=0.0039). Note that marker rs12474977 is 646 kb centromeric to marker rs7729084, and the two markers were adjacent to each other on the panel. The marker on Chromosome 8 that was associated with the greatest excess African ancestry in both the case-only () and case-control analyses was rs4367565 (case-only and case-control p<0.02).
Genomewide admixture mapping results in 482 men with prostate cancer, adjusted for age
Summary of SNPs at regional ancestry association peaks with |Z| >3.0
Admixture mapping results from select chromosomes in 482 African American men with prostate cancer, adjusted for age. (A) Chromosome 7 (B) Chromosome 5 (C) Chromosome 8
When subjects were stratified by age (<60 or ≥60), both age categories supported an association with rs2141360 on chromosome 7q31 (). Conversely, support for rs4367565 on chromosome 8q24 was greater in men in the older age group than in the younger age group (Z=2.063, p=0.039 vs. Z=1.513, p=0.13). Overall, the greatest ancestry association observed in the men < age 60 was at rs6724395 on chromosome 2p14, in a region of excess European ancestry (Z=−4.195, p=0.000027). The greatest excess African ancestry in men < age 60 occurred at rs692842, approximately 1.9 Mb from the peak on chromosome 5 in the unstratified sample. Among men ≥ age 60, the greatest excess European ancestry was observed at rs2141360 on chromosome 7q31 (Z=−3.311, p=0.00090); note that this is also where a regional peak in the entire sample occurred. In this same subsample, the greatest excess African ancestry was observed at rs9288952 on chromosome 3 (Z=3.208, p=0.0013).
Within the HFHS subjects, we were able to stratify on prostate cancer aggressiveness in 238 cases with available clinical information. In the 134 men with aggressive disease, the strongest ancestry association was at the same marker on chromosome 7q31.31 (Z=−4.782, p=0.0000017), however no association with this marker was observed in the 104 men with non-aggressive disease (Z=−1.561, p=0.12, data not shown).