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Editorial |

Unwrapping the Implications of BRCA1 and BRCA2 Mutations in Ovarian Cancer

David M. Hyman, MD; David R. Spriggs, MD
JAMA. 2012;307(4):408-410. doi:10.1001/jama.2012.24.
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Three large studies have demonstrated improved survival in BRCA -associated ovarian cancers compared with sporadic ovarian cancers.13 These trials have combined BRCA1 and BRCA2 mutation carriers because of the relative rarity of BRCA1 and BRCA2 mutations, which only account for approximately 10% and 5% of unselected cases of serous ovarian cancer, respectively.4 However, although both mutations are associated with hereditary breast and ovarian cancers, it has been suggested that these cancer predisposition syndromes represent related but clinically distinct entities.5 The lifetime risk of ovarian cancer is higher in BRCA1 than BRCA2 mutation carriers, estimated at 36% to 60% and 16% to 27%, respectively.6,7BRCA1 mutation carriers tend to develop ovarian cancer on average approximately 8 years earlier than BRCA2 mutation carriers.1,4 Microarrays of BRCA1 - and BRCA2 -associated ovarian cancers also show significant differences in gene expression.8 Moreover, the protection conferred by risk-reducing salpingo-oophorectomy against breast and gynecological cancers may differ between carriers of BRCA1 and BRCA2 mutations.9

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