TY - JOUR
T1 - A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany
AU - Maier, Christiane
AU - Herkommer, Kathleen
AU - Hoegel, Josef
AU - Vogel, Walther
AU - Paiss, Thomas
N1 - Funding Information:
We want to thank all patients, their families and attending urologists for contributing to this study. We gratefully acknowledge Petra Reutter and Margot Brugger for technical assistance. This work was supported by the Deutsche Krebshilfe, grant number 70-3111-V03 and in part by NCI Grant #U01 CA89600-02.
PY - 2005/3
Y1 - 2005/3
N2 - Prostate cancer is a complex disease with a substantial genetic contribution involved in the disease risk. Several genomewide linkage studies conducted so far have demonstrated a strong heterogeneity of susceptibility. In order to assess candidate regions that are particularly relevant for the German population, we performed a genomewide linkage search on 139 prostate cancer families. A nonparametric method (ZIr scores), using GENEHUNTERPLUS, was applied at 500 markers (panel P1400, deCODE), with an average spacing of 7.25 cM. In the entire family collection, linkage was most evident at 8p22 (ZIr = 2.47, P = 0.0068), close to the previously identified susceptibility gene MSR1. Further local maxima with ZIr > 2 (P<0.025) were observed at 1q, 5q and 15q. In a subgroup of 47 families, which matched the Johns Hopkins criteria of hereditary prostate cancer, suggestive linkage was found on 1p31 (ZIr = 3.37, P=0.00038), a previously not described candidate region. The remaining 92 pedigrees, with no strong disease history, revealed a maximum ZIr = 3.15 (P = 0.00082) at 8q13, possibly indicating a gene with reduced penetrance or recessive inheritance. Our results suggest pronounced locus heterogeneity of prostate cancer susceptibility in Germany. In the present study population, the MSR1 gene could play a significant role. Other conspicuous loci, like 1p31 and 8q13, need further investigation in order to verify their relevance and to identify candidate genes.
AB - Prostate cancer is a complex disease with a substantial genetic contribution involved in the disease risk. Several genomewide linkage studies conducted so far have demonstrated a strong heterogeneity of susceptibility. In order to assess candidate regions that are particularly relevant for the German population, we performed a genomewide linkage search on 139 prostate cancer families. A nonparametric method (ZIr scores), using GENEHUNTERPLUS, was applied at 500 markers (panel P1400, deCODE), with an average spacing of 7.25 cM. In the entire family collection, linkage was most evident at 8p22 (ZIr = 2.47, P = 0.0068), close to the previously identified susceptibility gene MSR1. Further local maxima with ZIr > 2 (P<0.025) were observed at 1q, 5q and 15q. In a subgroup of 47 families, which matched the Johns Hopkins criteria of hereditary prostate cancer, suggestive linkage was found on 1p31 (ZIr = 3.37, P=0.00038), a previously not described candidate region. The remaining 92 pedigrees, with no strong disease history, revealed a maximum ZIr = 3.15 (P = 0.00082) at 8q13, possibly indicating a gene with reduced penetrance or recessive inheritance. Our results suggest pronounced locus heterogeneity of prostate cancer susceptibility in Germany. In the present study population, the MSR1 gene could play a significant role. Other conspicuous loci, like 1p31 and 8q13, need further investigation in order to verify their relevance and to identify candidate genes.
KW - Familial
KW - Genomewide linkage
KW - Hereditary
KW - MSR1
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=14944363626&partnerID=8YFLogxK
U2 - 10.1038/sj.ejhg.5201333
DO - 10.1038/sj.ejhg.5201333
M3 - Article
C2 - 15536476
AN - SCOPUS:14944363626
SN - 1018-4813
VL - 13
SP - 352
EP - 360
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 3
ER -
