Increased cancer risks for relatives of very early-onset breast cancer cases with and without BRCA1 and BRCA2 mutations.
BACKGROUND
Little is known regarding cancer risks for relatives of women with very early-onset breast cancer.


METHODS
We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth.


RESULTS
For relatives of carriers, the female breast cancer SIRs were 13.13 (95% CI 6.57-26.26) and 12.52 (5.21-30.07) for BRCA1 and BRCA2, respectively. The ovarian cancer SIR was 12.38 (3.1-49.51) for BRCA1 and the prostate cancer SIR was 18.55 (4.64-74.17) for BRCA2. For relatives of non-carriers, the SIRs for female breast, prostate, lung, brain and urinary cancers were 4.03 (2.91-5.93), 5.25 (2.50-11.01), 7.73 (4.74-12.62), 5.19 (2.33-11.54) and 4.35 (1.81-10.46), respectively. For non-carriers, the SIRs remained elevated and were statistically significant for breast and prostate cancer when based on verified cancers.


CONCLUSIONS
First-degree relatives of women with very early-onset breast cancer are at increased risk of cancers not explained by BRCA1 and BRCA2 mutations.
Dite
G S
GS
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Level 1, 723 Swanston Street, Melbourne, Carlton VIC 3053, Australia.
Whittemore
A S
AS
Knight
J A
JA
John
E M
EM
Milne
R L
RL
Andrulis
I L
IL
Southey
M C
MC
McCredie
M R E
MR
Giles
G G
GG
Miron
A
A
Phipps
A I
AI
West
D W
DW
Hopper
J L
JL
D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D009035:Mothers; D009154:Mutation; D012306:Risk; D035781:Siblings