BRCA1 mutations and prostate cancer in Poland.
Evidence to date that BRCA1 mutation carriers are at an increased risk of prostate cancer is mixed - both positive and negative studies have been published. To establish whether or not inherited variation in BRCA1 influences prostate cancer risk we genotyped 1793 men with prostate cancer in Poland and 4570 controls for three founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.45% of the cases and 0.48% of the controls (odds ratio=0.9; P=1.0). The odds ratios varied substantially by mutation. The 5382insC mutation is the most common of the three founder mutations. It was detected only in one case (0.06%), whereas it was seen in 0.37% of controls (P=0.06). In contrast, the 4153delA was more common in prostate cancer cases (0.22%) than in controls (0.04%) (odds ratio=5.1; 95% confidence interval: 0.9-27.9; P=0.1). The C61G mutation was also found in excess in cases (0.17%) compared with controls (0.07%) (odds ratio=2.6; 95% confidence interval: 0.5-12.7; P=0.5). Eight men with prostate cancer carried a mutation. Only one of these carried the 5382insC mutation, compared with 17 of 22 individuals with mutations in the control population (P=0.003). These data suggest that the 5382insC mutation is unlikely to be pathogenic for prostate cancer in the Polish population. The presence of one of the other alleles was associated with an increased risk for prostate cancer (odds ratio=3.6; 95% confidence interval: 1.1-11.3; P=0.045); in particular for familial prostate cancer (odds ratio=12; 95% confidence interval: 2.9-51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers varies with the position of the mutation.
Cybulski
Cezary
C
Department of Genetics and Pathology, International Hereditary Cancer Center, Poland. cezarycy@sci.pam.szczecin.pl
Górski
Bohdan
B
Gronwald
Jacek
J
Huzarski
Tomasz
T
Byrski
Tomasz
T
Debniak
Tadeusz
T
Jakubowska
Anna
A
Wokołorczyk
Dominika
D
Gliniewicz
Bartłomiej
B
Sikorski
Andrzej
A
Stawicka
Małgorzata
M
Godlewski
Dariusz
D
Kwias
Zbigniew
Z
Antczak
Andrzej
A
Krajka
Kazimierz
K
Lauer
Wojciech
W
Sosnowski
Marek
M
Sikorska-Radek
Paulina
P
Bar
Krzysztof
K
Klijer
Robert
R
Romuald
Zdrojowy
Z
Małkiewicz
Bartosz
B
Borkowski
Andrzej
A
Borkowski
Tomasz
T
Szwiec
Marek
M
Posmyk
Michal
M
Narod
Steven A
SA
Lubiński
Jan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010375:Pedigree; D011044:Poland / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
D019313:BRCA1 Protein