Parity, oral contraceptives, and the risk of ovarian cancer among carriersand noncarriers of a BRCA1 or BRCA2 mutation

Background Multiparity and the use of oral contraceptives reduce the risk o f ovarian cancer, but their effects on this risk in women with a BRCA1 or B RCA2 mutation are unclear. Methods We conducted a population-based case control study of ovarian cance r among Jewish women in Israel. Women were tested for the two founder mutat ions in BRCA1 and the one founder mutation in BRCA2 that are known to be co mmon among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate a nalyses that included all control women, who did not have ovarian cancer. Results Of 751 controls who underwent mutation analysis, 13 (1.7 percent) h ad 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 birt h and each additional year of use of oral contraceptives were found to lowe r the risk of ovarian cancer, as expected. Additional births were protectiv e in separate analyses of carriers and non-carriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the r eduction 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 m utation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral c ontraceptives for the chemoprevention of ovarian cancer in carriers of such mutations. (N Engl J Med 2001;345:235-40.) Copyright (C) 2001 Massachusett s Medical Society.