In the news

Gayther et al have tested for mutations in the BRCA1 and BRCA2 genes in one affected member from each of 112 families containing at least two first- or second-degree relatives affected by epithelial ovarian cancer [Gayther, S.A. et al. (1999) Am J Hum Genet 65, 1021-1029 (Abstract); see Breast cancer summary for background information]. They found BRCA1 mutations in 36% of the families and BRCA2 mutations in 7%. To assess whether another locus might be responsible for cancer in the remaining 57% of families, they performed segregation analysis assuming the existence of a third locus and using known or estimated values for such parameters as the maximum total frequency of breast cancer susceptibility alleles, the age-specific risk of breast and ovarian cancer, the sensitivity of mutation detection, the familial ovarian cancer risk in first -degree relatives observed in epidemiological studies, and the national incidence of ovarian cancer. Although the existence of other familial ovarian cancer susceptibility genes could not be excluded, they concluded that chance clustering of sporadic ovarian cases in some families, combined with the limited sensitivity of mutation detection, may account for most or all of the families in which BRCA1 or 2 mutations were not found.

Comment: As the prognosis for ovarian cancer is poor, early detection is vital. The risks conferred by BRCA1 and 2 mutations are sufficiently high to justify preventive oophorectomy once the woman's family is complete. The findings of this study have implications for the identification of families in whom genetic testing may be useful. Gayther et al, in their discussion, comment that "testing for predisposing mutations is likely to be justified in any family in which two or more close relatives have epithelial ovarian cancer and that testing should be directed first at the BRCA1 gene and, if this is negative, the BRCA2 gene". The question of what to do if no mutation is found, however, remains unanswered.