Abstract
Prostate cancer (PrCa) is the most common male cancer in developed countries and the second most common cause of cancer death after lung cancer. We recently reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families, which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The aim of this study was to identify and to detect other loci linked to HPC. Here we used ordered subset analysis (OSA), conditioned on nonparametric linkage to these loci to detect other loci linked to HPC in subsets of families, but not the overall sample. We analyzed the families based on their evidence for linkage to chromosome 2, chromosome 17 and a maximum score using the strongest evidence of linkage from either of the two loci. Significant linkage to a 5-cM linkage interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on Xq26.3-q27 (ΔLOD=3.193, empirical P=0.009) was observed in a subset of 41 families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were novel to the analysis combining linkage evidence from both primary loci were identified; 18q12.1-q12.2 (OSA LOD=2.541, ΔLOD=1.651, P=0.03) and 22q11.1-q11.21 (OSA LOD=2.395, ΔLOD=2.36, P=0.006), which is close to HPC6. Using OSA allows us to find additional loci linked to HPC in subsets of families, and underlines the complex genetic heterogeneity of HPC even in highly aggregated families.
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Acknowledgements
We would like to express our gratitude to the families who participated in this study. This work was supported in part by the Intramural Program of the National Human Genome Research Institute, National Institutes of Health, the Academy of Finland (116437, 251074), the Sigrid Juselius Foundation, the Finnish Cancer Organizations and the Competitive Research Funding of the Tampere University Hospital (9M094). CDC is the recipient of an NHGRI Health Disparities Research Fellowship. The International Consortium for Prostate Cancer Genetics (ICPCG), including the consortium’s Data Coordinating Center (DCC), is made possible by a grant from the National Institutes of Health U01 CA89600 (to William B Isaacs). SNP genotyping services were provided by the Center for Inherited Disease Research (NIH Contract: N01-HG-65403).
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Simpson, C., Cropp, C., Wahlfors, T. et al. Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis. Eur J Hum Genet 21, 437–443 (2013). https://doi.org/10.1038/ejhg.2012.185
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DOI: https://doi.org/10.1038/ejhg.2012.185
