OMEN WHO HAVE IN-herited mutations in the BRCA1 or BRCA2 (BRCA1/2) genes have substantially elevated risks of breast cancer and ovarian cancer, with a lifetime risk of breast cancer of 56% to 84%. [1][2][3] The estimated ovarian cancer risks range from 36% to 63% for BRCA1 mutation carriers and 10% to 27% for BRCA2 mutation carriers. [3][4][5][6] Women who are mutation carriers have cancer risk-management options that include risk-reducing salpingooophorectomy, risk-reducing mastectomy, annual cancer screening, and chemoprevention. Due to the lack of effective screening for ovarian cancer, salpingo-oophorectomy is strongly recommended once childbearing is complete.Salpingo-oophorectomy has been demonstrated to decrease the risk of both breast cancer and ovarian cancer in BRCA1/2 mutation carriers. [7][8][9][10][11][12][13][14][15][16] However, estimates for risk and mortality reduction for women with and without For editorial comment see p 1011.

BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRAD51. Results presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and colocalize in subnuclear foci in somatic cells and on the axial elements of developing synaptonemal complexes. Like BRCA1 and RAD51, BRCA2 relocates to PCNA+ replication sites following exposure of S phase cells to hydroxyurea or UV irradiation. Thus, BRCA1 and BRCA2 participate, together, in a pathway(s) associated with the activation of double-strand break repair and/or homologous recombination. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer.

Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.