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Type: Journal article
Title: Report of endometrial cancer in Australian BRCA1 and BRCA2 mutation-positive families
Author: Duffy, D.
Antill, Y.
Stewart, C.
Young, J.
Spurdle, A.
Citation: Twin Research and Human Genetics, 2011; 14(2):111-118
Publisher: Cambridge University Press (CUP)
Issue Date: 2011
ISSN: 1832-4274
1839-2628
Statement of
Responsibility: 
David L. Duffy, Yoland C. Antill, Colin J. Stewart, Joanne P. Young, kConFab, and Amanda B. Spurdle
Abstract: There is evidence that tamoxifen treatment of BRCA1 and BRCA2 carriers for prior breast cancer increases risk of endometrioid subtype endometrial cancer (EC), and suggestive evidence that BRCA1 and BRCA2 mutation carriers may be predisposed to EC in the absence of tamoxifen exposure. We assessed the association of EC with BRCA1 or BRCA2 mutation status in Australasian breast-ovarian families. Report of at least one case of EC was significantly greater in BRCA1-positive families (35/218 (16%); p = .03) and non-significantly greater in BRCA2-positive families (23/189 (12%); p = .6), compared to high-risk breast cancer families without a BRCA1/2 mutation (86/796 (11%)). EC was the first/concurrent cancer for 41% of EC cases with multiple cancer diagnoses from BRCA1/2 families, and early onset for most of these diagnoses. Mutation status was imputed for ungeno-typed individuals from 57 BRCA1/2 pedigrees reporting EC using BRCAPRO. Effects of genotype on EC diagnosis age, and interaction with tamoxifen therapy, were assessed using Cox proportional hazards regression analysis. EC risk was non-significantly marginally greater for BRCA1 carriers (hazard ratio = 1.25, 95%CI = 0.65-2.41), and BRCA2 carriers (HR = 1.12, 95%CI = 0.51-2.45), compared to non-carrier family members. Tamoxifen therapy was highly significantly associated with EC (HR = 6.68, 95%CI = 3.12-15.15; p = 1.7 x 10(-6)) in BRCA1/2 families, with no evidence for interaction between tamoxifen therapy and BRCA1/2 genotype. Our family-based study supports a 7-fold increase in EC risk with tamoxifen exposure for female family members from BRCA1/2 families. Early onset EC in carriers without tamoxifen use suggests that further study is required to assess association of modest EC risk with BRCA1/2 mutation status alone.
Keywords: BRCA1; BRCA2; endometrial cancer; tamoxifen
Rights: © Cambridge University Press 2011
RMID: 0030012030
DOI: 10.1375/twin.14.2.111
Grant ID: http://purl.org/au-research/grants/nhmrc/145684
http://purl.org/au-research/grants/nhmrc/288704
http://purl.org/au-research/grants/nhmrc/454508
Appears in Collections:Medicine publications

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