Mendelian inheritance of familial prostate cancer

Bob S. Carter, Terri L Beaty, Gary D. Steinberg, Barton Childs, Patrick Walsh

Research output: Contribution to journalArticle

Abstract

Previous studies have demonstrated familial clustering of prostate cancer. To define the nature of this familial aggregation and to assess whether Mendelian inheritance can explain prostate cancer clustering, proportional hazards and segregation analyses were performed on 691 families ascertained through a single prostate cancer proband. The proportional hazards analyses revealed that two factors, early age at onset of disease in the proband and multiple affected family members, were important determinants of risk prostate cancer in these families. Furthermore, segregation analyses revealed that this clustering can be best explained by tosomal dominant inheritance of a rare (q = 0.0030) high-risk allele leading to an early onset of prostate cancer. The estimated cumulative risk of prostate cancer for carriers releted that the allele was highly penetrant: by age 85, 88% of carriers compared to only 5% of noncarriers are projected to affected with prostate cancer. The best fitting autosomal dominant model further suggested that this inherited form of prostate cancer accounts for a significant proportion of early onset disease but overall is responsible for a small proportion of prostate cancer occurrence (9% by age 85). These data provide evidence that prostate cancer is inherited in Mendelian fashion in a subset of families and provide a foundation for gene mapping studies of heritable prostate cancer. Characterization of genes involved in inherited prostate cancer could provide important insight into the development of this disease in general.

Original languageEnglish (US)
Pages (from-to)3367-3371
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number8
StatePublished - 1992

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Prostatic Neoplasms
Cluster Analysis
Familial Prostate cancer
Alleles
Chromosome Mapping
Age of Onset

Keywords

  • Autosomal dominant inheritance
  • Genetic epidemiology
  • Segregation analysis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mendelian inheritance of familial prostate cancer. / Carter, Bob S.; Beaty, Terri L; Steinberg, Gary D.; Childs, Barton; Walsh, Patrick.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 8, 1992, p. 3367-3371.

Research output: Contribution to journalArticle

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AU - Walsh, Patrick

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N2 - Previous studies have demonstrated familial clustering of prostate cancer. To define the nature of this familial aggregation and to assess whether Mendelian inheritance can explain prostate cancer clustering, proportional hazards and segregation analyses were performed on 691 families ascertained through a single prostate cancer proband. The proportional hazards analyses revealed that two factors, early age at onset of disease in the proband and multiple affected family members, were important determinants of risk prostate cancer in these families. Furthermore, segregation analyses revealed that this clustering can be best explained by tosomal dominant inheritance of a rare (q = 0.0030) high-risk allele leading to an early onset of prostate cancer. The estimated cumulative risk of prostate cancer for carriers releted that the allele was highly penetrant: by age 85, 88% of carriers compared to only 5% of noncarriers are projected to affected with prostate cancer. The best fitting autosomal dominant model further suggested that this inherited form of prostate cancer accounts for a significant proportion of early onset disease but overall is responsible for a small proportion of prostate cancer occurrence (9% by age 85). These data provide evidence that prostate cancer is inherited in Mendelian fashion in a subset of families and provide a foundation for gene mapping studies of heritable prostate cancer. Characterization of genes involved in inherited prostate cancer could provide important insight into the development of this disease in general.

AB - Previous studies have demonstrated familial clustering of prostate cancer. To define the nature of this familial aggregation and to assess whether Mendelian inheritance can explain prostate cancer clustering, proportional hazards and segregation analyses were performed on 691 families ascertained through a single prostate cancer proband. The proportional hazards analyses revealed that two factors, early age at onset of disease in the proband and multiple affected family members, were important determinants of risk prostate cancer in these families. Furthermore, segregation analyses revealed that this clustering can be best explained by tosomal dominant inheritance of a rare (q = 0.0030) high-risk allele leading to an early onset of prostate cancer. The estimated cumulative risk of prostate cancer for carriers releted that the allele was highly penetrant: by age 85, 88% of carriers compared to only 5% of noncarriers are projected to affected with prostate cancer. The best fitting autosomal dominant model further suggested that this inherited form of prostate cancer accounts for a significant proportion of early onset disease but overall is responsible for a small proportion of prostate cancer occurrence (9% by age 85). These data provide evidence that prostate cancer is inherited in Mendelian fashion in a subset of families and provide a foundation for gene mapping studies of heritable prostate cancer. Characterization of genes involved in inherited prostate cancer could provide important insight into the development of this disease in general.

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