Variation of breast cancer risk among BRCA1/2 carriers.
BACKGROUND
The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers.


OBJECTIVE
To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics.


METHODS
Probands were identified from a population-based, case-control study (Women's Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years.


METHODS
Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families.


RESULTS
Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P = .04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P = .28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics.


CONCLUSIONS
There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations.
Begg
Colin B
CB
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. beggc@mskcc.org
Haile
Robert W
RW
Borg
Ake
A
Malone
Kathleen E
KE
Concannon
Patrick
P
Thomas
Duncan C
DC
Langholz
Bryan
B
Bernstein
Leslie
L
Olsen
Jørgen H
JH
Lynch
Charles F
CF
Anton-Culver
Hoda
H
Capanu
Marinela
M
Liang
Xiaolin
X
Hummer
Amanda J
AJ
Sima
Cami
C
Bernstein
Jonine L
JL
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009154:Mutation; D012306:Risk