Israel-NCI Study* of the Use of Oral Contraceptives and Risk of Ovarian Cancer in Women with Alterations in BRCA1 or BRCA2 Genes

National Cancer Institute
Wednesday, 25 July 2001

1. What was the purpose of the study?

There is clear evidence that use of oral contraceptives (birth control pills) reduces the risk of ovarian cancer in the general population. The purpose of the current study was to evaluate whether the use of oral contraceptives reduces the risk of ovarian cancer in women with specific alterations in BRCA1 and BRCA2 genes. Women with these alterations are at much higher risk of ovarian cancer than other women.

2. Who were the study participants?

The study involved 840 Israeli women with ovarian cancer and 751 controls. All were tested for two mutations in BRCA1 (185delAG and 5382insC) and one in BRCA2 (6174delT), alterations commonly present in Jews from eastern or central Europe. The women were asked about their use of birth control pills and their reproductive histories.

3. What is the main finding?

The researchers found that for women with alterations in BRCA1 or BRCA2 genes, the use of oral contraceptives did not increase or decrease their risk of ovarian cancer. In agreement with previous studies, however, they did observe that for women without the alterations, the use of contraceptives lowered the ovarian cancer risk.

4. What are the implications of this study for women who are considering using oral contraceptives?

This study supports previous reports that the use of oral contraceptives will reduce the risk of ovarian cancer in the vast majority of women. Women without extensive histories of breast and ovarian cancer in their families should continue to make individual decisions as they always have.

The current report suggests that oral contraceptives are not effective in lowering the risk of ovarian cancer in women with alterations in BRCA1 or BRCA2 genes. However, at this point, a definite conclusion is premature. Additional research is needed to confirm or refute these findings. Another consideration is that oral contraceptives may increase the risk of breast cancer in women with these alterations (see question 9).

The net impact for each woman must be assessed individually, taking into account not only the possible cancer risks, but also the availability and desirability of other contraceptive options. Women concerned about the potential risks of oral contraceptive use should consult with their health care providers about their options.

5. Does this mean that women should get themselves tested for these mutations before using oral contraceptives?

Having a genetic test has economic, psychological, as well as possible insurance implications. The vast majority of women should make decisions about oral contraceptive use on the basis of their reproductive choices. Women with several close family members who have had breast or ovarian cancer should consult with their health care provider about their options.

6. What are the other important findings of the study?

The researchers found that with each additional child, the risk of ovarian cancer was reduced for women with and without these particular alterations in BRCA1 and BRCA2 genes.

7. Is there information from other studies on the effects of use of oral contraceptives and the number of children on the risk of ovarian cancer in women with these gene alterations?

In 1998, Narod et al from The Hereditary Breast Cancer Clinical Study Group reported in the New England Journal of Medicine that for women with one of these alterations, both factors -- using birth control pills and having children -- reduce the risk of ovarian cancer.

8. Why do the results of the two studies differ?

It is not clear why the results from the Israeli-NCI study differ from those from the Hereditary Breast Cancer Clinical Study Group. The reason could be related to the characteristics of the study participants, the statistical methods used, or chance. The Study Group involved women from families with large numbers of breast and ovarian cancers while the Israeli-NCI study did not focus exclusively on women from cancer-prone families. Further research will resolve this question.

9. What are the effects of birth control pills on the risk of breast cancer?

This study does not address the risk of breast cancer. Previous studies have shown that oral contraceptives do not affect the risk of breast cancer in women overall. There is some evidence, however, that the use of oral contraceptives may increase the risk of breast cancer in women with these alterations.

10. How many cases of ovarian cancers are due to these genetic alterations?

Of the approximately 23,000 cases of ovarian cancer diagnosed annually in the United States, about 5 percent (1,000) are due to an alteration in BRCA1 or BRCA2 genes.

Of the women in the Israeli-NCI study, 29 percent of the women with ovarian cancer and 1.7 percent of the women without ovarian cancer had an alteration in one of these genes.

11. How many people in the United States have alterations in these genes?

The number is not known precisely. The best estimate is that between 0.1 percent and 0.6 percent of people in the U.S. population have an alteration in one of these genes.

12. Do only Jews have these particular alterations?

No. But a relatively high percentage (2.3 percent) of American Jews from eastern or central Europe have one of three specific alterations tested for in this study.

In 1994, one of these alterations (185delAG) in BRCA1 was the first found to be associated with a particular ethnic group. Since then, a few other alterations have been reported to occur in other ethnic groups (Icelandic, Norwegian, and Dutch), and are now being studied. In general, over 100 different alterations scattered throughout BRCA1 have been found, and nearly that many in BRCA2. Most of these have been discovered in cancer-prone families.

13. Why was the study done in Israel?

The frequency of these three particular gene alterations is much higher in the general Israeli population than in the general U.S. population. Therefore, the frequency of these mutations is also much higher in women with ovarian cancer in Israel than in women with ovarian cancer in the United States. This higher frequency enabled the researchers to complete the study more quickly in Israel than in the United States.

14. Is this study relevant to American women, particularly those who are not Jewish?

The researchers believe that the factors that affect ovarian cancer risk in Israeli women are likely to affect women in other countries. They also believe that the impact of oral contraceptives is likely to be similar for women with these particular alterations as well as for women with other alterations in BRCA1 and BRCA2, regardless of geography or ethnic background.

*The study is titled "Effects of Parity and Use of Oral Contraceptives on the Risk of Ovarian Cancer Among Carriers and Noncarriers of a BRCA1 or BRCA2 Mutation. The authors are Baruch Modan, Patricia Hartge, Galit Hirsh-Yechezkel, Angela Chetrit, Flora Lubin, Uzi Beller, Gilad Ben-Baruch, Amiram Fishman, Joseph Menczer, Eitan Friedman, Benjamin Piura, Sara M. Ebbers, Jeffery P. Struewing, Margaret A. Tucker, and Sholom Wacholder for the National Israel Ovarian Cancer Study Group. New Engl J Med 2001;345:235-240.

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