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Moslehi et al have tested for the presence of three mutations in the BRCA1 and BRCA2 genes that are particularly common in Ashkenazi Jewish populations [Moslehi, R. et al (2000 Am J Hum Genet 66, 1259-1272; see Breast cancer summary for background information]. Collectively, these mutations are found in about 2% of such populations. Of 213 unselected Ashkenazi Jewish women with ovarian cancer ascertained from 11 medical centres in North America and Israel, 41% were found to carry one of the three mutations. Other studies suggest that in the wider population (for example, the UK population as a whole) the  percentage of women carrying BRCA1 or 2 mutations is much smaller, probably less than 5%. Moslehi et al estimate that the three mutations they studied "account for most of the heritability of ovarian cancer in the Jewish population". Penetrances calculated for the three mutations were 51% for 185delAG, 21% for 5382insC (both BRCA1 mutations) and 14% for 6174delT (a BRCA2 mutation). First degree relatives of mutation carriers also had a significantly increased risk of breast or ovarian disease: the relative risk of ovarian cancer by the age of 75, for example, was about 5-6.

Comment: This paper demonstrates clearly how different population groups can, usually because of founder effects, show very different degrees of genetic risk for specific diseases. It is generally thought not to be worthwhile screening all women with ovarian cancer for BRCA1 or BRCA2 mutations, but the work of Moslehi et al and others suggests that the picture may be rather different in the Ashkenazi Jewish population. Offering genetic testing to the first-degree relatives of mutation-positive women, with the option of prophylactic ooporectomy if they also test positive, may be justified, though Moslehi et al comment that better information about the effectiveness and risks of prophylactic oophorectomy is needed.