although the corrected OR estimates are smaller than the uncorrected OR, most of them are still larger than the OR estimates from the replication study. Of the 11 SNPs, 10 selection-adjusted CIs are consistent with those from the replication estimates (Table 4). The difference observed in the point estimates could be explained by the enriched nature of the cases and controls in stage 1. In the initial study, cases were selected as being were diagnosed through clinical symptoms rather than through routine screening by prostate-specific antigen (PSA) in order to maximize the proportion of cases that cause morbidity and mortality. Also these cases are genetically ‘enriched’ by including men diagnosed by age 60 years or having a family history of prostate cancer, as such individuals are thought to be more likely to carry susceptibility alleles, thereby increasing statistical power [Eeles et al., 2008]. These enriched genetic cases may have comparatively stronger genetic risk compared to controls, leading to higher ORs than in the replication study.
