Discovery last month of two genes implicated in early-onset breastand ovarian cancer left a 10 to 15 percent blank spot on the mapconfronting young women at risk of these familial malignancies.That spot shrunk Saturday with announcement in The Lancet thatFrench scientists have pinned down a third susceptibility locus.Unlike BRCA1 and BRCA2, the first two genes, their presumedBRCA3 apparently does not reside on human chromosome 13.Oncologists and geneticists at INSERM, the French NationalInstitute of Health and Medical Research in Marseilles, carried outlinkage analysis on 37 women in five extended French families withhistories of breast or ovarian cancer. They were selected by criteriathat minimized a possible role for BRCA1 in their genomicbackground, and subsequent analysis ruled out BRCA2 for four ofthe five pedigrees.All of the families, the letter to Lancet reported, contained six ormore affected members, at least one of whom under age 55 did notmatch up with the first two genes. Hence, the researchersconcluded, "This panel of families is an important resource to mapthe putative BRCA3 gene."Genetic factors contribute to an estimated 5 percent of all breastcancers, but 25 percent of the early-onset cases diagnosed beforeage 30.Geneticist Mark Scolnick, vice president of research at MyriadGenetics, in Salt Lake City, a co-discoverer of BRCA1, toldBioWorld Today in September that genes one and two account for"about 40 to 45 percent each of the early onset cases, leaving 10 to15 percent representing a third gene." (For more on BRCA1, seeBioWorld Today, Sept. 15, 16 and 17, p. 1.)The French researchers suggested that "the proportion of familiesthat is not linked to BRCA1 or to BRCA2 may be higher thanpreviously expected." n102494BRCA3

-- David N. Leff Science Editor

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