Women with a pathogenic mutation in the BRCA1 or BRCA2 genes have a high lifetime risk of ovarian cancer. For carriers of BRCA1 mutations, the risk is about 40%; for BRCA2 carriers, the risk is about 25%.

Proposed strategies for reducing the risk of ovarian cancer include prophylactic oophorectomy (removal of the ovaries), chemoprevention with oral contraceptives, and regular ultrasound screening.

However, there are concerns that oral contraceptive use could be associated with an increased risk of breast cancer, and the effectiveness of ovarian cancer screening has not been established.

In several previous case-control and prospective studies, tubal ligation has been associated with a decreased risk of invasive epithelial ovarian cancer.

Steven Narod and colleagues from Sunnybrook and Women's College Hospital, Toronto, Canada, aimed to assess the potential of tubal ligation in reducing the risk of ovarian cancer in women who carry predisposing mutations in the BRCA1 or BRCA2 genes.

The investigators did a matched case-control study among women from Canada, the USA and the UK who had undergone genetic testing and who carried a pathogenic mutation in BRCA1 or BRCA2 genes.

The cases were 232 women with a history of invasive ovarian cancer; controls were 232 women without ovarian cancer who had both ovaries intact. Cases and controls were matched for year of birth, country of residence and mutation (BRCA1 or BRCA2).

Among BRCA1 carriers, significantly fewer cases than controls had ever had tubal ligation (30 of 173 [18%] compared with 60 of 173 [35%]).

The relative risk of ovarian cancer after tubal ligation decreased by 60%, and by 72% for women who had tubal ligation and had a history of oral contraceptive use; furthermore, these risk reductions were long-lasting. No protective effect of tubal ligation was seen among carriers of the BRCA2 mutation.

Steven Narod comments: "Currently, many women choose to undergo oophorectomy to prevent ovarian cancer. The age at which oophorectomy is done should take into account the woman's desire to preserve fertility, the level of protection offered against breast and ovarian cancer, and the consequences of surgical menopause.

"Few women choose to have oophorectomy before age 35 years, but offering tubal ligation as soon as childbearing is complete is reasonable, and can be followed by an oophorectomy at a later date. We believe that tubal ligation is associated with a reduction in risk of ovarian cancer in women who carry BRCA1 mutations.

"For maximum protection, tubal ligation should be considered in combination with oral contraceptives, oophorectomy, or both. We cannot yet make specific recommendations for carriers of BRCA2, and further studies are needed for this subgroup."

(Reference: The Lancet, 12th May 2001.)

[Contact: Marie MacPherson]

14-May-2001