Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: results from the International BRCA1/2 Carrier Cohort Study.
BACKGROUND
Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated in a small number of studies.


METHODS
We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox proportional hazards framework.


RESULTS
There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had ever used OC were at a significantly reduced risk of developing ovarian cancer (hazard ratio, 0.52; 95% confidence intervals, 0.37-0.73; P = 0.0002) and increasing duration of OC use was associated with a reduced ovarian cancer risk (P trend = 0.0004). The protective effect of OC use for BRCA1 mutation carriers seemed to be greater among more recent users. Tubal ligation was associated with a reduced risk of ovarian cancer for BRCA1 carriers (hazard ratio, 0.42; 95% confidence intervals, 0.22-0.80; P = 0.008). The number of ovarian cancer cases in BRCA2 mutation carriers was too small to draw definitive conclusions.


CONCLUSIONS
The results provide further confirmation that OC use, number of full-term pregnancies, and tubal ligation are associated with ovarian cancer risk in BRCA1 carriers to a similar relative extent as in the general population.
Antoniou
Antonis C
AC
Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK. antonis@srl.cam.ac.uk
Rookus
Matti
M
Andrieu
Nadine
N
Brohet
Richard
R
Chang-Claude
Jenny
J
Peock
Susan
S
Cook
Margaret
M
Evans
D Gareth
DG
Eeles
Rosalind
R
Nogues
Catherine
C
Faivre
Laurence
L
Gesta
Paul
P
van Leeuwen
Flora E
FE
Ausems
Margreet G E M
MG
Osorio
Ana
A
Caldes
Trinidad
T
Simard
Jacques
J
Lubinski
Jan
J
Gerdes
Anne-Marie
AM
Olah
Edith
E
Fürhauser
Christine
C
Olsson
Hakan
H
Arver
Brita
B
Radice
Paolo
P
Easton
Douglas F
DF
Goldgar
David E
DE
D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D015331:Cohort Studies; D003276:Contraceptives, Oral / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D010298:Parity; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors; D013246:Sterilization, Tubal
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D003276:Contraceptives, Oral