August 21, 2001 Access past issues

Reviewed by: Matthew R. Kurumada, Mindy Clyne, Muin J. Khoury Office of Genomics and Disease Prevention, CDC

The Health Outcome

Multiparity and the use of oral contraceptives have been previously shown to decrease the risk of ovarian cancer   BRCA1 and BRCA2 mutations are associated with increased risk of ovarian cancer with lifetime risks of less than 15%-50%. It is not clear, however, whether or not multiparity and the use of oral contraceptives can reduce the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

The Finding

Modan et al. found that while increased parity did decrease ovarian cancer risk in carriers of a BRCA1 or BRCA2 mutation, increased duration of oral contraceptive use did not.  These results were found in a case-control study done in Israel among Jewish women (1).  A detailed abstraction of this article is available online as part of the HuGE Net e-journal club (2).  All pathologically confirmed cases of ovarian cancer or primary peritoneal carcinoma of possible ovarian origin that were diagnosed between March 1, 1994, and June 30, 1999, were enrolled in this study.  For each case subject, two control subjects were selected from the Central Population Registry and were matched for age, area of birth, and for geographic region and duration of residence in Israel.  Women who had previously undergone bilateral oophorectomy were excluded.  Information regarding parity and oral contraceptive use was obtained through interviews and mutation testing for two BRCA1 founder mutations (185delAG and 5382insC); one BRCA2 founder mutation (6174delT) was performed on DNA that was taken from blood samples and buccal cells and paraffin embedded tissue sections.  The authors concluded that for women carrying a BRCA1 or BRCA2 mutation, increased parity conferred a protective effect on ovarian cancer risk (odds ratio for parity of five or more births  = 0.38).  No significant findings were seen for duration of oral contraceptive use.  Among noncarriers, both increased parity and increased duration of oral contraceptive were protective for ovarian cancer risk.

Public Health Implications

These results presented are not consistent with a previous study (3) showing a reduction of ovarian cancer risk by oral contraceptive use in BRCA1 and BRCA2 mutation carriers. The main implication of this study is that it may be premature to prescribe oral contraceptives for carriers of BRCA1 and BRCA2 mutations until further research can elucidate any chemopreventive effects of oral contraceptive use, especially in light of the possible increased risk of breast cancer in these women. The report also demonstrates the difficulty of assessing joint effects of a rare genetic factor with environmental factors.

References

1. Modan B, Hartge P, Hirsch-Yechezkel G, et al. Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. New Engl J Med 2001;345:235-40.
2. E-journal club abstraction template
3. Narod SA, Risch H, Moslehi R, et al. Oral contraceptives and the risk of hereditary  ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. New Engl J Med 1998;339:424-28.