Genome-wide linkage analyses of hereditary prostate cancer families with colon cancer provide further evidence for a susceptibility locus on 15q11-q14

The search for susceptibility loci in hereditary prostate cancer (HPC) is challenging because of locus and disease heterogeneity. One approach to reduce disease heterogeneity is to stratify families on the basis of the occurrence of multiple cancer types. This method may increase the power for detecting susceptibility loci, including those with pleiotropic effects. We have completed a genome-wide SNP linkage analysis of 96 HPC families, each of which has one or more first-degree relatives with colon cancer (CCa), and further analyzed the subset of families with two or more CCa cases (n=27). When only a prostate cancer (PCa) phenotype was considered to be affected, we observed suggestive evidence for linkage (LOD >= 1.86) at 15q14, 18q21 and 19q13 in all families, and at 1p32 and 15q11-q14 in families with two or more CCa cases. When both the PCa and CCa phenotypes were considered affected, suggestive evidence for linkage was observed at 11q25, 15q14 and 18q21 in all families, and at 1q31, 11q14 and 15q11-14 in families with two or more CCa cases. The strongest linkage signal was identified at 15q14 when both PCa and CCa phenotypes were considered to be affected in families with two or more CCa cases (recessive HLOD=3.88). These results provide further support for the presence of HPC susceptibility loci on chromosomes 11q14, 15q11-q14 and 19q13 and highlight loci at 1q31, 11q, 15q11-14 and 18q21 as having possible pleiotropic effects. This study shows the benefit of using a comprehensive family cancer history to create more genetically homogenous subsets of HPC families for linkage analyses. European Journal of Human Genetics (2010) 18, 1141-1147; doi: 10.1038/ejhg.2010.49; published online 21 April 2010