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

Rebecca Berry, Daniel J Schaid, Jeffrey R. Smith, Amy J. French, Jennifer J. Schroeder, Shannon K. McDonnell, Brett J. Peterson, Zheng Yuan Wang, John D. Carpten, Steven G. Roberts, David J. Tester, Michael L. Blute, Jeffrey M. Trent, Stephen N Thibodeau

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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 1q2425 (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 ~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.

Original languageEnglish (US)
Pages (from-to)539-546
Number of pages8
JournalAmerican Journal of Human Genetics
Volume66
Issue number2
DOIs
StatePublished - 2000

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Chromosomes, Human, Pair 1
Prostatic Neoplasms
Brain Neoplasms
Inborn Genetic Diseases
Microsatellite Repeats
protein C activator peptide
Familial Prostate cancer
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer. / Berry, Rebecca; Schaid, Daniel J; Smith, Jeffrey R.; French, Amy J.; Schroeder, Jennifer J.; McDonnell, Shannon K.; Peterson, Brett J.; Wang, Zheng Yuan; Carpten, John D.; Roberts, Steven G.; Tester, David J.; Blute, Michael L.; Trent, Jeffrey M.; Thibodeau, Stephen N.

In: American Journal of Human Genetics, Vol. 66, No. 2, 2000, p. 539-546.

Research output: Contribution to journalArticle

Berry, R, Schaid, DJ, Smith, JR, French, AJ, Schroeder, JJ, McDonnell, SK, Peterson, BJ, Wang, ZY, Carpten, JD, Roberts, SG, Tester, DJ, Blute, ML, Trent, JM & Thibodeau, SN 2000, 'Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer', American Journal of Human Genetics, vol. 66, no. 2, pp. 539-546. https://doi.org/10.1086/302771
Berry, Rebecca ; Schaid, Daniel J ; Smith, Jeffrey R. ; French, Amy J. ; Schroeder, Jennifer J. ; McDonnell, Shannon K. ; Peterson, Brett J. ; Wang, Zheng Yuan ; Carpten, John D. ; Roberts, Steven G. ; Tester, David J. ; Blute, Michael L. ; Trent, Jeffrey M. ; Thibodeau, Stephen N. / Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer. In: American Journal of Human Genetics. 2000 ; Vol. 66, No. 2. pp. 539-546.
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title = "Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer",
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 1q2425 (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 ~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.",
author = "Rebecca Berry and Schaid, {Daniel J} and Smith, {Jeffrey R.} and French, {Amy J.} and Schroeder, {Jennifer J.} and McDonnell, {Shannon K.} and Peterson, {Brett J.} and Wang, {Zheng Yuan} and Carpten, {John D.} and Roberts, {Steven G.} and Tester, {David J.} and Blute, {Michael L.} and Trent, {Jeffrey M.} and Thibodeau, {Stephen N}",
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T1 - Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer

AU - Berry, Rebecca

AU - Schaid, Daniel J

AU - Smith, Jeffrey R.

AU - French, Amy J.

AU - Schroeder, Jennifer J.

AU - McDonnell, Shannon K.

AU - Peterson, Brett J.

AU - Wang, Zheng Yuan

AU - Carpten, John D.

AU - Roberts, Steven G.

AU - Tester, David J.

AU - Blute, Michael L.

AU - Trent, Jeffrey M.

AU - Thibodeau, Stephen N

PY - 2000

Y1 - 2000

N2 - 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 1q2425 (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 ~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.

AB - 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 1q2425 (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 ~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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