Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation.
BACKGROUND
Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear.


METHODS
We conducted a population-based case-control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer.


RESULTS
Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and noncarriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0.2 percent per year of oral-contraceptive use (-4.9 to 5.0 percent).


CONCLUSIONS
The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations.
Modan
B
B
Department of Clinical Epidemiology, Chaim Sheba Medical Center, Tel-Hashomer, Israel. BModan@gertner.health.gov.il
Hartge
P
P
Hirsh-Yechezkel
G
G
Chetrit
A
A
Lubin
F
F
Beller
U
U
Ben-Baruch
G
G
Fishman
A
A
Menczer
J
J
Struewing
J P
JP
Tucker
M A
MA
Wacholder
S
S
D000328:Adult; D000368:Aged; D024682:BRCA2 Protein; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000517:prevention & control*; D010298:Parity; D012306:Risk; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D003276:Contraceptives, Oral; D009363:Neoplasm Proteins; D014157:Transcription Factors