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. 2000 Feb;66(2):539-46.
doi: 10.1086/302771.

Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer

R Berry  1 , D J Schaid, J R Smith, A J French, J J Schroeder, S K McDonnell, B J Peterson, Z Y Wang, J D Carpten, S G Roberts, D J Tester, M L Blute, J M Trent, S N Thibodeau
Affiliations

Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer

R Berry et al. Am J Hum Genet. 2000 Feb.

Abstract

Recent studies suggest that hereditary prostate cancer (PRCA) is a complex disease, involving multiple susceptibility genes and variable phenotypic expression. Through linkage analysis, potential prostate cancer susceptibility loci have been mapped to 3 regions on chromosome 1. To investigate the reported linkage to these regions, we conducted linkage studies on 144 PRCA families by using microsatellite markers in regions 1q24-25 (HPC1) and 1q42.2-43 (PCAP). We also examined the 1p36 (CAPB) region in 13 PRCA families with at least one case of brain cancer. No significant evidence of linkage to the HPC1 or PCAP region was found when the entire data set was analyzed. However, weak evidence for linkage to HPC1 was observed in the subset of families with male-to-male transmission (n=102; maximum multipoint nonparametric linkage [NPL] 1.99, P=.03). Weak evidence for linkage with heterogeneity within this subset was also observed (HLOD 1.21, P=.02), with approximately 20% of families linked. Although not statistically significant, suggestive evidence for linkage to PCAP was observed for the families (n=21) that met the three criteria of male-to-male transmission, average age of diagnosis <66 years, and >/=5 affected individuals (maximum multipoint NPL 1.45, P=.08). There was no evidence for linkage to CAPB in the brain cancer-prostate cancer subset. These results strengthen the argument that prostate cancer is a heterogeneous disease and that multiple genetic and environmental factors may be important for its etiology.

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Figures

Figure 1
Figure 1
Multipoint NPL scores for the whole data set (n=144) and four subsets, on a six-marker map of the HPC1 region. The subsets are average age of diagnosis <66 years (n=67), at least five affected individuals (n=47), male-to-male transmission (n=102), and a combination (n=21) of <66 years, at least five affected, and male-to-male transmission.
Figure 2
Figure 2
Multipoint NPL scores for the whole data set (n=144) and for four subsets, on a six-marker map of the PCAP region. The subsets are average age of diagnosis <66 years (n=67), at least five affected individuals (n=47), male-to-male transmission (n=102), and a combination (n=21) of <66 years, at least five affected, and male-to-male transmission.
Figure 3
Figure 3
Multipoint NPL scores for the brain cancer–prostate cancer subset (n=13) on a 4-marker map of the CAPB region
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Genome Database, http://gdbwww.gdb.org (for markers D1S452, D1S212, D1S466, D1S158, D1S422, D1S413, D1S235, D1S2678, D1S2850, D1S2785, D1S321, D1S2842, D1S1597, D1S402, D1S407, and D1S507)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nim.nih.gov/omim (for prostate cancer [MIM 176807], HPC1 [MIM 601518], HPC2 [MIM 602759], HPCX [MIM 300147], and CAPB [MIM 603688])

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