A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis
Tekijät: Simpson CL, Cropp CD, Wahlfors T, George A, Jones MS, Harper U, Ponciano-Jackson D, Tammela T, Schleutker J, Bailey-Wilson JE
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2013
Journal: European Journal of Human Genetics
Tietokannassa oleva lehden nimi: EUROPEAN JOURNAL OF HUMAN GENETICS
Lehden akronyymi: EUR J HUM GENET
Numero sarjassa: 4
Vuosikerta: 21
Numero: 4
Aloitussivu: 437
Lopetussivu: 443
Sivujen määrä: 7
ISSN: 1018-4813
DOI: https://doi.org/10.1038/ejhg.2012.185
Tiivistelmä
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 (Delta LOD=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, Delta LOD=1.651, P=0.03) and 22q11.1-q11.21 (OSA LOD=2.395, Delta LOD=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. European Journal of Human Genetics (2013) 21, 437-443; doi:10.1038/ejhg.2012.185; published online 5 September 2012
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 (Delta LOD=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, Delta LOD=1.651, P=0.03) and 22q11.1-q11.21 (OSA LOD=2.395, Delta LOD=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. European Journal of Human Genetics (2013) 21, 437-443; doi:10.1038/ejhg.2012.185; published online 5 September 2012
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