The protective effects against ovarian cancer of parity and oral contraceptive use differ depending on whether women have mutations of the BRCA1 or the BRCA2 gene, according to a study of Jewish women in Israel.¹ Nearly one-third (29%) of women in this population with ovarian cancer have a BRCA1 or BRCA2 mutation, while fewer than 2% of those without ovarian cancer have such mutations. Overall, women who have had children and those who have used oral contraceptives for five or more years have a significantly lower likelihood of developing ovarian cancer than other women. However, while multiparity is protective against the risk of ovarian cancer for both women with BRCA1 or BRCA2 mutations and those without, oral contraceptive use is protective only for women without mutations.

To investigate whether parity and the use of oral contraceptives are as protective against the risk of ovarian cancer in women with mutations of the BRCA1 or the BRCA2 gene as they are in women without such mutations, researchers identified all Jewish women in Israel who had ovarian cancer diagnosed between 1994 and 1999. Women who agreed to participate in the study were interviewed in the hospital, usually 4-6 days after gynecologic surgery. To assess the presence of BRCA1 or BRCA2 mutations, researchers collected blood samples from the participants for molecular testing.

For every study participant with ovarian cancer, researchers chose two controls with similar demographic backgrounds. Controls were interviewed in their homes, and samples were collected from them for molecular testing. The analysts compared the two groups of women using logistic regression, controlling for age, ethnic background, personal history of breast cancer, family history of breast or ovarian cancer, and a history of gynecologic surgery.

Out of the 1,707 women who received a diagnosis of ovarian cancer in Israel during the study period, 1,124 were interviewed and 840 underwent molecular testing; 2,257 women were included in the study as controls, 751 of whom underwent molecular testing. Twenty-nine percent of the women with ovarian cancer who underwent molecular testing were found to have a mutation of either the BRCA1 or the BRCA2 gene. In comparison, fewer than 2% of those without ovarian cancer had a mutation.

An analysis of the women who underwent molecular testing found that the risk of ovarian cancer decreased significantly with increasing number of births. Women who had had one or two births were 40% less likely than nulliparous women to develop ovarian cancer (odds ratio, 0.6), while women who had had three or more births had an even further reduction in risk (0.5). Women who had used oral contraceptives for five or more years were less likely than women who had never used oral contraceptives to develop ovarian cancer (0.7); each year of oral contraceptive use reduced the risk by 4%.

When researchers analyzed the incidence of ovarian cancer accounting for mutation status, they found that increasing parity (odds ratio, 0.5) and five or more years of oral contraceptive use (0.5) remained protective for women who did not have BRCA1 or BRCA2 mutations. Among women with BRCA1 or BRCA2 mutations, each birth was associated with a significant 12% decrease in the risk of ovarian cancer; there was no evidence of protective effects from the use of oral contraceptives.

The researchers point out that their findings do not agree with those from a previous study in regard to the protective effects of oral contraceptive use in women with BRCA1 or BRCA2 mutations. They surmise that this discrepancy could have occurred because they were able to directly compare the risk of ovarian cancer in women with and those without BRCA1 or BRCA2 mutations, while the previous study surveyed women at high risk, many of whom had undergone prophylactic surgery. In light of their data and the discrepancy in the literature, the researchers conclude that "it is premature to prescribe oral contraceptives for the chemoprevention of ovarian cancer in carriers of a BRCA1 or BRCA2 mutation."--J. Rosenberg

REFERENCE

1. Modan B et al., Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation, New England Journal of Medicine, 2001, 345(4):235-240.