Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer

Ilir Agalliu, Erika M. Kwon, Daniel Zadory, Laura McIntosh, Joseph Thompson, Janet L. Stanford, Elaine A. Ostrander

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose: Several epidemiologic studies have reported that carriers of germline mutations in the BRCA2 gene have an increased risk of prostate cancer, with the highest risk observed in men diagnosed at earlier ages. However, studies of the contribution of BRCA2 mutations to the etiology of hereditary prostate cancer (HPC) have been inconsistent. Experimental Design: To further address this issue, 266 subjects from 194 HPC families participating in the Seattle-based Prostate Cancer Genetic Research Study were screened for BRCA2 mutations by sequencing the coding regions, intron-exon boundaries, and suspected regulatory elements of this gene. Of selected HPC families, 32 had multiple breast or ovarian cancer cases, 16 were Jewish, 8 had a pancreatic cancer case, and 138 had at least one affected man diagnosed with prostate cancer at an early age (<60 years). Results: No disease-associated protein truncating BRCA2 mutations were found in 266 subjects from HPC families. There were 61 DNA sequence variants, of which 31 (50.8%) changed the predicted amino acids. No associations were found between these missense changes and family characteristics. Among affected men with prostate cancer, there were no statistically significant differences between the genotype frequencies of DNA variants with a minor allele frequency of 1% or higher and between the strata defined by median age at diagnosis or by clinical features. Conclusion: No evidence was found in this study for an association between BRCA2 mutations and susceptibility to HPC in men selected from high-risk families.

Original languageEnglish (US)
Pages (from-to)839-843
Number of pages5
JournalClinical Cancer Research
Volume13
Issue number3
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

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BRCA2 Gene
Germ-Line Mutation
Prostatic Neoplasms
Mutation
BRCA2 Protein
Genetic Research
Regulator Genes
Pancreatic Neoplasms
Gene Frequency
Ovarian Neoplasms
Introns
Epidemiologic Studies
Exons
Research Design
Genotype
Familial Prostate cancer
Breast Neoplasms
Amino Acids
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Agalliu, I., Kwon, E. M., Zadory, D., McIntosh, L., Thompson, J., Stanford, J. L., & Ostrander, E. A. (2007). Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer. Clinical Cancer Research, 13(3), 839-843. https://doi.org/10.1158/1078-0432.CCR-06-2164

Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer. / Agalliu, Ilir; Kwon, Erika M.; Zadory, Daniel; McIntosh, Laura; Thompson, Joseph; Stanford, Janet L.; Ostrander, Elaine A.

In: Clinical Cancer Research, Vol. 13, No. 3, 01.02.2007, p. 839-843.

Research output: Contribution to journalArticle

Agalliu, I, Kwon, EM, Zadory, D, McIntosh, L, Thompson, J, Stanford, JL & Ostrander, EA 2007, 'Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer', Clinical Cancer Research, vol. 13, no. 3, pp. 839-843. https://doi.org/10.1158/1078-0432.CCR-06-2164
Agalliu, Ilir ; Kwon, Erika M. ; Zadory, Daniel ; McIntosh, Laura ; Thompson, Joseph ; Stanford, Janet L. ; Ostrander, Elaine A. / Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 3. pp. 839-843.
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