Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer.
Studies of families who segregate BRCA2 mutations have found that men who carry disease-associated mutations have an increased risk of prostate cancer, particularly early-onset disease. A study of sporadic prostate cancer in the UK reported a prevalence of 2.3% for protein-truncating BRCA2 mutations among patients diagnosed at ages < or =55 years, highlighting the potential importance of this gene in prostate cancer susceptibility. To examine the role of protein-truncating BRCA2 mutations in relation to early-onset prostate cancer in a US population, 290 population-based patients from King County, Washington, diagnosed at ages <55 years were screened for germline BRCA2 mutations. The coding regions, intron-exon boundaries, and potential regulatory elements of the BRCA2 gene were sequenced. Two distinct protein-truncating BRCA2 mutations were identified in exon 11 in two patients. Both cases were Caucasian, yielding a mutation prevalence of 0.78% (95% confidence interval (95%CI) 0.09-2.81%) and a relative risk (RR) of 7.8 (95%CI 1.8-9.4) for early-onset prostate cancer in white men carrying a protein-truncating BRCA2 mutation. Results suggest that protein-truncating BRCA2 mutations confer an elevated RR of early-onset prostate cancer. However, we estimate that <1% of early-onset prostate cancers in the general US Caucasian population can be attributed to these rare disease-associated BRCA2 mutations.
Agalliu
I
I
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Karlins
E
E
Kwon
E M
EM
Iwasaki
L M
LM
Diamond
A
A
Ostrander
E A
EA
Stanford
J L
JL
D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data*; D017668:Age of Onset; D016022:Case-Control Studies; D005787:Gene Frequency; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D014861:Washington / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data*
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