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


METHODS
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.


CONCLUSIONS
No evidence was found in this study for an association between BRCA2 mutations and susceptibility to HPC in men selected from high-risk families.
Agalliu
Ilir
I
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, USA.
Kwon
Erika M
EM
Zadory
Daniel
D
McIntosh
Laura
L
Thompson
Joseph
J
Stanford
Janet L
JL
Ostrander
Elaine A
EA
D017668:Age of Onset; D000483:Alleles; D004252:DNA Mutational Analysis; D005091:Exons; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk