Multiple newly identified loci associated with prostate cancer susceptibility. Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M,

This association study, and the two following, were an important follow-up to association studies linking discrete genetic loci (SNPs or single nucleotide polymorphisms) to prostate cancer risk. All of these studies are large (thousands of subjects) and use genome-wide approaches to identify the regions associated with risk. The three studies confirm that the previously reported loci on chromosomes 8q24 and 17q are associated with prostate cancer risk. This study from DeCODE genetics narrowed their search to the X chromosome because of the higher incidence of prostate cancer noted in brothers, and identified a marker on Xp11.22, independent of a previously reported marker HPCX, that was strongly associated with prostate cancer risk. They validated this finding in five of seven independent large patient cohorts. By comparing “aggressive” to “nonaggressive” cancers (defined by fairly broad criteria) the locus on chromosome 2p15 was found. It was validated in only two of seven independent samples, although a combined analysis showed a highly significant association. The statistical power and multiple attempts at validation in this study are its strengths.