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Ovarian cancer in BRCA1/2 mutation carriers: The impact of mutation position and family history on the cancer risk.

Abstract：

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.

journal_name

Maturitas

journal_title

Maturitas

authors

Teixeira N,Mourits MJ,Vos JR,Kolk DM,Jansen L,Oosterwijk JC,Bock GH

doi

10.1016/j.maturitas.2015.07.001

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

197-202

issue

2

eissn

0378-5122

issn

1873-4111

pii

S0378-5122(15)30008-6

journal_volume

82

pub_type

杂志文章

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