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Radiation Treatment, ATM, BRCA1/2, and CHEK2*1100delC Pathogenic Variants and Risk of Contralateral Breast Cancer.
- Source :
-
Journal of the National Cancer Institute [J Natl Cancer Inst] 2020 Dec 14; Vol. 112 (12), pp. 1275-1279. - Publication Year :
- 2020
-
Abstract
- Whether radiation therapy (RT) affects contralateral breast cancer (CBC) risk in women with pathogenic germline variants in moderate- to high-penetrance breast cancer-associated genes is unknown. In a population-based case-control study, we examined the association between RT; variants in ATM, BRCA1/2, or CHEK2*1100delC; and CBC risk. We analyzed 708 cases of women with CBC and 1399 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2000 and aged younger than 55 years at diagnosis and screened for variants in breast cancer-associated genes. Rate ratios (RR) and 95% confidence intervals (CIs) were estimated using multivariable conditional logistic regression. RT did not modify the association between known pathogenic variants and CBC risk (eg, BRCA1/2 pathogenic variant carriers without RT: RR = 3.52, 95% CI = 1.76 to 7.01; BRCA1/2 pathogenic variant carriers with RT: RR = 4.46, 95% CI = 2.96 to 6.71), suggesting that modifying RT plans for young women with breast cancer is unwarranted. Rare ATM missense variants, not currently identified as pathogenic, were associated with increased risk of RT-associated CBC (carriers of ATM rare missense variants of uncertain significance without RT: RR = 0.38, 95% CI = 0.09 to 1.55; carriers of ATM rare missense variants of uncertain significance with RT: RR = 2.98, 95% CI = 1.31 to 6.80). Further mechanistic studies will aid clinical decision-making related to RT.<br /> (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Case-Control Studies
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Heterozygote
Humans
Middle Aged
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local pathology
Neoplasms, Radiation-Induced etiology
Neoplasms, Radiation-Induced genetics
Neoplasms, Second Primary genetics
Penetrance
Radiotherapy adverse effects
Sequence Deletion
Young Adult
Ataxia Telangiectasia Mutated Proteins genetics
BRCA1 Protein genetics
BRCA2 Protein genetics
Breast Neoplasms genetics
Breast Neoplasms pathology
Breast Neoplasms radiotherapy
Checkpoint Kinase 2 genetics
Neoplasm Recurrence, Local etiology
Neoplasms, Second Primary etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2105
- Volume :
- 112
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 32119081
- Full Text :
- https://doi.org/10.1093/jnci/djaa031