Risk for contralateral breast cancer among carriers of the CHEK21100delC mutation in the WECARE Study

L Mellemkjaer; C Dahl; J H Olsen; L Bertelsen; P Guldberg; J Christensen; A-L Børresen-Dale; M Stovall; B Langholz; L Bernstein; C F Lynch; K E Malone; R W Haile; M Andersson; D C Thomas; P Concannon; M Capanu; J D   Boice Jr; J L Bernstein; WECARE Study Collaborative Group

doi:10.1038/sj.bjc.6604228

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Risk for contralateral breast cancer among carriers of the CHEK21100delC mutation in the WECARE Study

Journal article

Open access

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Risk for contralateral breast cancer among carriers of the CHEK21100delC mutation in the WECARE Study

L Mellemkjaer, C Dahl, J H Olsen, L Bertelsen, P Guldberg, J Christensen, A-L Børresen-Dale, M Stovall, B Langholz, L Bernstein, …

British journal of cancer, Vol.98(4), pp.728-733

02/26/2008

DOI: 10.1038/sj.bjc.6604228

PMCID: PMC2259175

PMID: 18253122

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Abstract

The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985--1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR)=1.8, 95% confidence interval (CI)=0.6-5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI=0.8-8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population.

SEER Program

Humans

Middle Aged

Risk Factors

Protein-Serine-Threonine Kinases - genetics

Genotype

Germ-Line Mutation - genetics

Case-Control Studies

Breast Neoplasms - radiotherapy

Breast Neoplasms - genetics

Checkpoint Kinase 2

Female

Protein-Serine-Threonine Kinases - metabolism

Breast Neoplasms - epidemiology

Details

Title: Subtitle: Risk for contralateral breast cancer among carriers of the CHEK21100delC mutation in the WECARE Study
Creators: L Mellemkjaer - Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. lene@cancer.dk
C Dahl
J H Olsen
L Bertelsen
P Guldberg
J Christensen
A-L Børresen-Dale
M Stovall
B Langholz
L Bernstein
C F Lynch
K E Malone
R W Haile
M Andersson
D C Thomas - University of Southern California
P Concannon
M Capanu
J D Boice Jr
J L Bernstein
WECARE Study Collaborative Group
Resource Type: Journal article
Publication Details: British journal of cancer, Vol.98(4), pp.728-733
DOI: 10.1038/sj.bjc.6604228
PMID: 18253122
PMCID: PMC2259175
NLM abbreviation: Br J Cancer
ISSN: 0007-0920
eISSN: 1532-1827
Publisher: England
Grant note: N01PC35142 / NCI NIH HHS R01 CA129639 / NCI NIH HHS N02 PC015105 / NCI NIH HHS U01 CA083178 / NCI NIH HHS U55/CCR921930-02 / PHS HHS N01-PC-35142 / NCI NIH HHS N01PC35139 / NCI NIH HHS R01 CA114236 / NCI NIH HHS N02-PC15105 / NCI NIH HHS N01-PC35143 / NCI NIH HHS N01PC35143 / NCI NIH HHS R01 CA097397 / NCI NIH HHS N01-PC-35139 / NCI NIH HHS
Language: English
Date published: 02/26/2008
Academic Unit: Epidemiology
Record Identifier: 9983995109302771

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