ArticleAmerican journal of human genetics2009
Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer.
Article in American journal of human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.
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Who cites it
111 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Penetrance of ATM Gene Mutations in Breast Cancer: A Meta-Analysis of Different Measures of Risk.Genetic epidemiology · 2016Pooled it
- Association of three SNPs in TOX3 and breast cancer risk: Evidence from 97275 cases and 128686 controls.Scientific reports · 2015Pooled it
- Trial
- Genome stability disrupted by the circRBM39(4,5,6)-RPA2 axis represses breast tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- Deep learning analysis of breast cancer histology predicts ATM pathogenic variant carrier status.NPJ digital medicine · 2026Article
- Genomic landscape of hereditary cancer syndromes in the largest cohort in Colombia: a retrospective study.Lancet regional health. Americas · 2026Article
- Association of gene variant type and location with breast cancer risk in the general population.Annals of oncology : official journal of the European Society for Medical Oncology · 2025Article
- Breast tumors from ATM pathogenic variant carriers display a specific genome-wide DNA methylation profile.Breast cancer research : BCR · 2025Article
- Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population.Breast cancer research : BCR · 2025Article
- Multifocal neuromuscular hamartoma with smooth muscle and Schwannian components.BMJ case reports · 2024Article
- Germline Variant Spectrum in Southern Italian High-Risk Hereditary Breast Cancer Patients: Insights from Multi-Gene Panel Testing.Current issues in molecular biology · 2024Article
- Article
- Safety of the Breast Cancer Adjuvant Radiotherapy in Ataxia-Telangiectasia Mutated Variant Carriers.Cancers · 2024Article
- Gender-Specific Genetic Predisposition to Breast Cancer:Cancers · 2024Review
- Uncovering the clinical relevance of unclassified variants in DNA repair genes: a focus onFrontiers in genetics · 2024Article
- Germline variants associated with breast cancer in Khakass women of North Asia.Molecular biology reports · 2023Article
- ATM c.7570G>C is a high-risk allele for breast cancer.International journal of cancer · 2023Article
- ATM suppresses c-Myc overexpression in the mammary epithelium in response to estrogen.Cell reports · 2023Article
- Mild Neurological Phenotype Associated with Hypomorphic Variants in the Ataxia-Telangiectasia Mutated Gene.Movement disorders clinical practice · 2023Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors.
Funding
Abstract
The susceptibility gene for ataxia telangiectasia, ATM, is also an intermediate-risk breast-cancer-susceptibility gene. However, the spectrum and frequency distribution of ATM mutations that confer increased risk of breast cancer have been controversial. To assess the contribution of rare variants in this gene to risk of breast cancer, we pooled data from seven published ATM case-control mutation-screening studies, including a total of 1544 breast cancer cases and 1224 controls, with data from our own mutation screening of an additional 987 breast cancer cases and 1021 controls. Using an in silico missense-substitution analysis that provides a ranking of missense substitutions from evolutionarily most likely to least likely, we carried out analyses of protein-truncating variants, splice-junction variants, and rare missense variants. We found marginal evidence that the combination of ATM protein-truncating and splice-junction variants contribute to breast cancer risk. There was stronger evidence that a subset of rare, evolutionarily unlikely missense substitutions confer increased risk. On the basis of subset analyses, we hypothesize that rare missense substitutions falling in and around the FAT, kinase, and FATC domains of the protein may be disproportionately responsible for that risk and that a subset of these may confer higher risk than do protein-truncating variants. We conclude that a comparison between the graded distributions of missense substitutions in cases versus controls can complement analyses of truncating variants and help identify susceptibility genes and that this approach will aid interpretation of the data emerging from new sequencing technologies.
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