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Ovarian cancer in BRCA1/2 mutation carriers: The impact of mutation position and family history on the cancer risk. | LitMetric
Objectives : Assessing the combined impact of mutation position, regarding the ovarian cancer cluster region (OCCR), and type of cancer family history (FH) on age-related penetrance of ovarian cancer (OC) in women from BRCA1/2 families from the northern Netherlands.Study Design : A consecutive series of 1763 mutation carriers and their first-degree relatives from 355 proven BRCA1/2 families with a history of breast and/or ovarian cancer with in total 248 OC cases was included. Mutations were stratified for gene (BRCA1 or BRCA2) and location (within or outside the OCCR). FH was stratified for type of cancer occurring in first and second-degree relatives (OC only, breast cancer (BC) only or both OC and BC).Main Outcome Measures : Cox-proportional hazard models were applied to estimate the OCCR effect, including and excluding a FH of cancer.Results : Among BRCA1 families, OC risks were higher in women with OCCR mutations versus those with non-OCCR mutations (HR=1.59, 95%CI=1.19-2.12). This effect remained significant after adjustment for the type of FH (HR=1.50, 95%CI=1.11-2.01). In BRCA2 families, mutation position did not significantly affect the OC risk (HR=1.50, 95%CI=0.74-3.04). However, in the BRCA2 group, a FH including only OC presented by itself a strong impact on OC risk (HR=4.63, 95%CI=2.38-9.02), which remained stable after adjustment for mutation position (HR=4.48, 95%CI=2.28-8.81).Conclusion : OCCR mutations significantly increased the OC risk in BRCA1 families regardless of the type of FH, but in BRCA2 families, type of FH seems to have a higher impact than mutation position on OC risk.
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