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Gene-gene interactions in breast cancer susceptibility
- Source :
- Human Molecular Genetics, 21, 958-62, Human Molecular Genetics, 21, 4, pp. 958-62
- Publication Year :
- 2012
-
Abstract
- There have been few definitive examples of gene-gene interactions in humans. Through mutational analyses in 7325 individuals, we report four interactions (defined as departures from a multiplicative model) between mutations in the breast cancer susceptibility genes ATM and CHEK2 with BRCA1 and BRCA2 (case-only interaction between ATM and BRCA1/BRCA2 combined, P = 5.9 × 10 -4; ATM and BRCA1, P= 0.01; ATM and BRCA2, P= 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 × 10 =4; CHEK2 and BRCA1, P= 0.01; CHEK2 and BRCA2, P= 0.01). The interactions are such that the resultant risk of breast cancer is lower than the multiplicative product of the constituent risks, and plausibly reflect the functional relationships of the encoded proteins in DNA repair. These findings have important implications for models of disease predisposition and clinical translation. © The Author 2011. Published by Oxford University Press. All rights reserved.
- Subjects :
- endocrine system diseases
DNA repair
DNA Mutational Analysis
Genes, BRCA2
Genes, BRCA1
Breast Neoplasms
Cell Cycle Proteins
DCN PAC - Perception action and control
Ataxia Telangiectasia Mutated Proteins
Protein Serine-Threonine Kinases
Biology
medicine.disease_cause
Breast cancer
Gene interaction
Genetics
medicine
Genetic predisposition
Humans
Genetic Predisposition to Disease
skin and connective tissue diseases
Molecular Biology
CHEK2
Genetics (clinical)
Family Health
Mutation
Models, Genetic
Tumor Suppressor Proteins
Association Studies Articles
General Medicine
medicine.disease
BRCA2 Protein
United Kingdom
Pedigree
DNA-Binding Proteins
Checkpoint Kinase 2
Cancer research
Female
Subjects
Details
- ISSN :
- 09646906
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....85e2e848dd3a7371734c7f0d366d6cf5