Population Genetic Testing for Cancer Susceptibility: Founder Mutations to Genomes

Overview

Journal Nat Rev Clin Oncol

Specialty Oncology

Date 2015 Oct 21

PMID 26483301

Citations 53

Authors

William D Foulkes

Bartha Maria Knoppers

Clare Turnbull

Affiliations

Soon will be listed here.

Abstract

The current standard model for identifying carriers of high-risk mutations in cancer-susceptibility genes (CSGs) generally involves a process that is not amenable to population-based testing: access to genetic tests is typically regulated by health-care providers on the basis of a labour-intensive assessment of an individual's personal and family history of cancer, with face-to-face genetic counselling performed before mutation testing. Several studies have shown that application of these selection criteria results in a substantial proportion of mutation carriers being missed. Population-based genetic testing has been proposed as an alternative approach to determining cancer susceptibility, and aims for a more-comprehensive detection of mutation carriers. Herein, we review the existing data on population-based genetic testing, and consider some of the barriers, pitfalls, and challenges related to the possible expansion of this approach. We consider mechanisms by which population-based genetic testing for cancer susceptibility could be delivered, and suggest how such genetic testing might be integrated into existing and emerging health-care structures. The existing models of genetic testing (including issues relating to informed consent) will very likely require considerable alteration if the potential benefits of population-based genetic testing are to be fully realized.

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References

ODonoghue C, Eklund M, Ozanne E, Esserman L . Aggregate cost of mammography screening in the United States: comparison of current practice and advocated guidelines. Ann Intern Med. 2014; 160(3):145. PMC: 4142190. DOI: 10.7326/M13-1217. View

Metcalfe K, Mian N, Enmore M, Poll A, Llacuachaqui M, Nanda S . Long-term follow-up of Jewish women with a BRCA1 and BRCA2 mutation who underwent population genetic screening. Breast Cancer Res Treat. 2012; 133(2):735-40. DOI: 10.1007/s10549-011-1941-0. View

Burke W, Coughlin S, Lee N, Weed D, Khoury M . Application of population screening principles to genetic screening for adult-onset conditions. Genet Test. 2002; 5(3):201-11. DOI: 10.1089/10906570152742245. View

Moyer V . Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013; 160(4):271-81. DOI: 10.7326/M13-2747. View

Narod S, Risch H, Moslehi R, Dorum A, Neuhausen S, Olsson H . Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med. 1998; 339(7):424-8. DOI: 10.1056/NEJM199808133390702. View

Plevritis S, Kurian A, Sigal B, Daniel B, Ikeda D, Stockdale F . Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA. 2006; 295(20):2374-84. DOI: 10.1001/jama.295.20.2374. View

Hilbers F, Vreeswijk M, van Asperen C, Devilee P . The impact of next generation sequencing on the analysis of breast cancer susceptibility: a role for extremely rare genetic variation?. Clin Genet. 2013; 84(5):407-14. DOI: 10.1111/cge.12256. View

Metcalfe K, Poll A, Royer R, Nanda S, Llacuachaqui M, Sun P . A comparison of the detection of BRCA mutation carriers through the provision of Jewish population-based genetic testing compared with clinic-based genetic testing. Br J Cancer. 2013; 109(3):777-9. PMC: 3738109. DOI: 10.1038/bjc.2013.309. View

King M, Levy-Lahad E, Lahad A . Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award. JAMA. 2014; 312(11):1091-2. DOI: 10.1001/jama.2014.12483. View

10.

Gabai-Kapara E, Lahad A, Kaufman B, Friedman E, Segev S, Renbaum P . Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proc Natl Acad Sci U S A. 2014; 111(39):14205-10. PMC: 4191771. DOI: 10.1073/pnas.1415979111. View

11.

Metcalfe K, Poll A, Llacuachaqui M, Nanda S, Tulman A, Mian N . Patient satisfaction and cancer-related distress among unselected Jewish women undergoing genetic testing for BRCA1 and BRCA2. Clin Genet. 2010; 78(5):411-7. DOI: 10.1111/j.1399-0004.2010.01499.x. View

12.

Green R, Berg J, Grody W, Kalia S, Korf B, Martin C . ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013; 15(7):565-74. PMC: 3727274. DOI: 10.1038/gim.2013.73. View

13.

Milne R, Antoniou A . Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers. Ann Oncol. 2011; 22 Suppl 1:i11-7. DOI: 10.1093/annonc/mdq660. View

14.

Howard H, Knoppers B, Cornel M, Clayton E, Senecal K, Borry P . Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes. Eur J Hum Genet. 2015; 23(12):1593-600. PMC: 4795188. DOI: 10.1038/ejhg.2014.289. View

15.

Kurian A, Ford J . Multigene Panel Testing in Oncology Practice: How Should We Respond?. JAMA Oncol. 2015; 1(3):277-8. DOI: 10.1001/jamaoncol.2015.28. View

16.

Metcalfe K, Poll A, Royer R, Llacuachaqui M, Tulman A, Sun P . Screening for founder mutations in BRCA1 and BRCA2 in unselected Jewish women. J Clin Oncol. 2009; 28(3):387-91. DOI: 10.1200/JCO.2009.25.0712. View

17.

Ball D, Harper P . Presymptomatic testing for late-onset genetic disorders: lessons from Huntington's disease. FASEB J. 1992; 6(10):2818-9. DOI: 10.1096/fasebj.6.10.1386046. View

18.

Narod S . Genetic Testing for BRCA Mutations Today and Tomorrow-About the ABOUT Study. JAMA Oncol. 2015; 1(9):1225-6. DOI: 10.1001/jamaoncol.2015.3269. View

19.

Evans D, Gareth E, Kesavan N, Nisha K, Lim Y, Yit L . MRI breast screening in high-risk women: cancer detection and survival analysis. Breast Cancer Res Treat. 2014; 145(3):663-72. DOI: 10.1007/s10549-014-2931-9. View

20.

Plon S, Eccles D, Easton D, Foulkes W, Genuardi M, Greenblatt M . Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat. 2008; 29(11):1282-91. PMC: 3075918. DOI: 10.1002/humu.20880. View