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Breast Cancer Research
Published in: Breast Cancer Research 1/2022

01-12-2022 | Breast Cancer | Short report

Population-based estimates of age-specific cumulative risk of breast cancer for pathogenic variants in ATM

Authors: Anne-Laure Renault, James G. Dowty, Jason A. Steen, Shuai Li, Ingrid M. Winship, Graham G. Giles, John L. Hopper, Melissa C. Southey, Tú Nguyen-Dumont

Published in: Breast Cancer Research | Issue 1/2022

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Abstract

Background

Multigene panel tests for breast cancer predisposition routinely include ATM as it is now a well-established breast cancer predisposition gene.

Methods

We included ATM in a multigene panel test applied to the Australian Breast Cancer Family Registry (ABCFR), a population-based case–control–family study of breast cancer, with the purpose of estimating the prevalence and penetrance of heterozygous ATM pathogenic variants from the family data, using segregation analysis.

Results

The estimated breast cancer hazard ratio for carriers of pathogenic ATM variants in the ABCFR was 1.32 (95% confidence interval 0.45–3.87; P = 0.6). The estimated cumulative risk of breast cancer to age 80 years for heterozygous ATM pathogenic variant carriers was estimated to be 13% (95% CI 4.6–30).

Conclusions

Although ATM has been definitively identified as a breast cancer predisposition gene, further evidence, such as variant-specific penetrance estimates, are needed to inform risk management strategies for carriers of pathogenic variants to increase the clinical utility of population testing of this gene.
Appendix
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Literature
1.
Couch FJ, Shimelis H, Hu C, Hart SN, Polley EC, Na J, Hallberg E, Moore R, Thomas A, Lilyquist J, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 2017;3(9):1190–6.CrossRef
2.
LaDuca H, Polley EC, Yussuf A, Hoang L, Gutierrez S, Hart SN, Yadav S, Hu C, Na J, Goldgar DE, et al. A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients. Genet Med. 2020;22(2):407–15.CrossRef
3.
Southey MC, Goldgar DE, Winqvist R, Pylkas K, Couch F, Tischkowitz M, Foulkes WD, Dennis J, Michailidou K, van Rensburg EJ et al: PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. J Med Genet. 2016.
4.
Bernstein JL, Teraoka S, Southey MC, Jenkins MA, Andrulis IL, Knight JA, John EM, Lapinski R, Wolitzer AL, Whittemore AS, et al. Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066–6T>G (IVS10-6T>G) from the Breast Cancer Family Registry. Hum Mutat. 2006;27(11):1122–8.CrossRef
5.
Goldgar DE, Healey S, Dowty JG, Da Silva L, Chen X, Spurdle AB, Terry MB, Daly MJ, Buys SM, Southey MC, et al. Rare variants in the ATM gene and risk of breast cancer. Breast Cancer Res. 2011;13(4):R73.CrossRef
6.
Dorling L, Carvalho S, Allen J, Gonzalez-Neira A, Luccarini C, Wahlstrom C, Pooley KA, Parsons MT, Fortuno C, Wang Q, et al. Breast cancer risk genes - association analysis in more than 113,000 women. N Engl J Med. 2021;384(5):428–39.CrossRef
7.
Hu C, Hart SN, Gnanaolivu R, Huang H, Lee KY, Na J, Gao C, Lilyquist J, Yadav S, Boddicker NJ et al (2021) A population-based study of genes previously implicated in breast cancer. New Engl J Med
8.
Nguyen-Dumont T, Dowty JG, Steen JA, Renault A-L, Hammet F, Mahmoodi M, Theys D, Rewse A, Tsimiklis H, Winship IM, et al. Population-based estimates of the age-specific cumulative risk of breast cancer for pathogenic variants in CHEK2: findings from the Australian Breast Cancer Family Registry. Cancers. 2021;13(6):1378.CrossRef
9.
Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfoldi J, Wang Q, Collins RL, Laricchia KM, Ganna A, Birnbaum DP, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434–43.CrossRef
10.
Tavtigian SV, Byrnes GB, Goldgar DE, Thomas A. Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications. Hum Mutat. 2008;29(11):1342–54.CrossRef
11.
Ferlay J, Steliarova-Foucher E, Forman D. Cancer incidence in five continents, CI5plus: IARC Cancer Base No. 9; 2014.
12.
Lesueur F, Easton DF, Renault AL, Tavtigian SV, Bernstein JL, Kote-Jarai Z, Eeles RA, Plaseska-Karanfia D, Feliubadalo L, Spanish ATMwg et al. First international workshop of the ATM and cancer risk group (4–5 December 2019). Fam Cancer 2021.
13.
Tavtigian SV, Oefner PJ, Babikyan D, Hartmann A, Healey S, Le Calvez-Kelm F, Lesueur F, Byrnes GB, Chuang S-C, Forey N, et al. Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. Am J Hum Genet. 2009;85(4):427–46.CrossRef
14.
Reyes KG, Clark C, Gerhart M, Newson AJ, Ormond KE. "I wish that there was more info": characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants. Fam Cancer 2021.
Metadata
Title
Population-based estimates of age-specific cumulative risk of breast cancer for pathogenic variants in ATM
Authors
Anne-Laure Renault
James G. Dowty
Jason A. Steen
Shuai Li
Ingrid M. Winship
Graham G. Giles
John L. Hopper
Melissa C. Southey
Tú Nguyen-Dumont
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2022
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-022-01518-y

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