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Genome linkage screen for prostate cancer susceptibility loci: Results from the Mayo Clinic familial prostate cancer study
Author(s) -
Cunningham Julie M.,
McDonnell Shan K.,
Marks Angela,
Hebbring Scott,
Anderson Sarah A.,
Peterson Brett J.,
Slager Susan,
French Amy,
Blute Michael L.,
Schaid Daniel J.,
Thibodeau Stephen N.
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10308
Subject(s) - pedigree chart , prostate cancer , genetic linkage , genetics , microsatellite , cancer , linkage (software) , biology , genetic heterogeneity , chromosome , prostate , medicine , gene , phenotype , allele
Prostate cancer is one of the most common cancers among men and has long been recognized to occur in familial clusters. Brothers and sons of affected men have a twofold to threefold increased risk of developing prostate cancer. However, identification of genetic susceptibility loci for prostate cancer has been extremely difficult. Several putative loci identified by genetic linkage have been reported to exist on chromosomes 1 (HPC1, PCAP, and CAPB), X (HPCX), 17 (HPC2), and 20 (HPC20), with genes RNASEL (HPC1) and ELAC2 (HPC2) tentatively defined. In this study, we report our genome linkage scan in 160 prostate cancer families, using the ABI Prism Linkage Mapping Set Version 2 with 402 microsatellite markers. The most significant linkage was found for chromosome 20, with a recessive model heterogeneity LOD score (HLOD) of 4.77, and a model‐free LOD score (LOD − ZLR) of 3.46 for the entire group of pedigrees. Linkage for chromosome 20 was most prominent among families with a late age of diagnosis (average age at diagnosis ≥ 66 years; maximum LOD − ZLR = 2.82), with <5 affected family members (LOD − ZLR = 3.02), with presence of hereditary prostate cancer (LOD − ZLR = 2.81), or with no male‐to‐male transmission of disease (LOD − ZLR = 3.84). No other chromosome showed significant evidence for linkage. However, chromosomes 6 and X showed suggestive results, with maximum LOD − ZLR values of 1.38 and 1.36, respectively. Subset analyses suggest additional chromosomal regions worth further follow‐up. Prostate 57: 335–346, 2003. © 2003 Wiley‐Liss, Inc.