Purpose of Review
Adolescents and young adults (AYAs) represent a unique patient cohort, straddling the realms of paediatric and adult medicine. AYA cancers may include traditionally “paediatric” cancers occurring at older than expected ages, or conversely, adult-onset cancers occurring at unusually young ages. Cancer incidence in AYAs (aged 15–39) is increasing, and disappointingly, survival data are worse than those in paediatric or older adult settings. Early recognition of underlying cancer predisposition syndromes (CPS) in AYAs may facilitate individualised therapies, initiation of tumour surveillance strategies and cascade testing in at-risk relatives. Increasingly, physicians together with the wider AYA multidisciplinary team recognise AYAs as a unique group that merit special considerations, particularly regarding the psychosocial impact of cancer and genetic diagnoses on self-identity, fertility and family planning.
AYA referral rates for genetic evaluation are suboptimal, but are improving with expanded access to testing, increasing clinician awareness and increasing public demand for genomic investigation.
Herein, we outline recent developments in CPS testing in the AYA cohort. We highlight clinical tools useful in identifying patients that may warrant genetic counselling and/or genetic testing. We also discuss AYA-specific ethical and psychosocial challenges of genetic testing.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
American Association for Cancer Research
Acute lymphoblastic leukaemia
American Society of Clinical Oncology
Adolescent(s) and young adult(s)
Cancer predisposition syndrome(s)
McGill Interactive Pediatric OncoGenetic Guidelines
Magnetic resonance imaging
National Health Service
Variant of uncertain significance
Wilms tumour, aniridia, genitourinary anomalies, intellectual disability
- WB MRI:
Whole-body magnetic resonance imaging
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Desandes E, Stark DP. Epidemiology of adolescents and young adults with cancer in Europe. Prog Tumor Res. 2016;43:1–15.
Aben KK, van Gaal C, van Gils NA, et al. Cancer in adolescents and young adults (15-29 years): a population-based study in the Netherlands 1989-2009. Acta Oncol. 2012;51(7):922–33.
CRUK. Cancer Research UK. Cancer Incidence Statistics. Cancer Incidence by age. [Available from: www.cancerresearchuk.org/health-professional/cancer-statistics/incidence. Accessed 13 Jan 2020.
•• Barr RD, Ries LA, Lewis DR, et al. Incidence and incidence trends of the most frequent cancers in adolescent and young adult Americans, including “nonmalignant/noninvasive” tumors. Cancer. 2016;122(7):1000–8 Overview of the epidemiology of cancer in AYAs in the USA.
Fidler MM, Gupta S, Soerjomataram I, Ferlay J, Steliarova-Foucher E, Bray F. Cancer incidence and mortality among young adults aged 20-39 years worldwide in 2012: a population-based study. Lancet Oncol. 2017;18(12):1579–89.
Bleyer A, Barr R, Hayes-Lattin B, Thomas D, Ellis C, Anderson B, et al. The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer. 2008;8(4):288–98.
Merks JH, Caron HN, Hennekam RC. High incidence of malformation syndromes in a series of 1,073 children with cancer. Am J Med Genet A. 2005;134A(2):132–43.
Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, et al. Germline mutations in predisposition genes in pediatric cancer. N Engl J Med. 2015;373(24):2336–46.
Grobner SN, Worst BC, Weischenfeldt J, et al. The landscape of genomic alterations across childhood cancers. Nature. 2018;555(7696):321–7.
Parsons DW, Roy A, Yang Y, et al. Diagnostic yield of clinical tumor and Germline whole-exome sequencing for children with solid tumors. JAMA Oncol. 2016;2(5):616–24.
Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst. 1999;91(11):943–9.
Rummel SK, Lovejoy L, Shriver CD, Ellsworth RE. Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer. Breast Cancer Res Treat. 2017;164(3):593–601.
Bayraktar S, Amendola L, Gutierrez-Barrera AM, Hashmi SS, Amos C, Gambello M, et al. Clinicopathologic characteristics of breast cancer in BRCA-carriers and non-carriers in women 35 years of age or less. Breast. 2014;23(6):770–4.
Sun J, Meng H, Yao L, Lv M, Bai J, Zhang J, et al. Germline mutations in cancer susceptibility genes in a large series of unselected breast cancer patients. Clin Cancer Res. 2017;23(20):6113–9.
Geredeli C, Yasar N, Sakin A. Germline mutations in BRCA1 and BRCA2 in breast cancer patients with high genetic risk in Turkish population. Int J Breast Cancer. 2019;2019:9645147.
Lin PH, Kuo WH, Huang AC, Lu YS, Lin CH, Kuo SH, et al. Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer. Oncotarget. 2016;7(7):8310–20.
• Copson ER, Maishman TC, Tapper WJ, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol. 2018;19(2):169–80 Frequency of BRCA variants in patients diagnosed with breast cancer under 40 years.
Kemp Z, Turnbull A, Yost S, Seal S, Mahamdallie S, Poyastro-Pearson E, et al. Evaluation of cancer-based criteria for use in mainstream BRCA1 and BRCA2 genetic testing in patients with breast cancer. JAMA Netw Open. 2019;2(5):e194428.
Stoffel EM, Koeppe E, Everett J, et al. Germline genetic features of young individuals with colorectal cancer. Gastroenterology. 2018;154(4):897–905 e1.
• Pearlman R, Frankel WL, Swanson B, et al. Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol. 2017;3(4):464–71 Overview of the germline predisposition to colorectal cancer in AYAs.
Mork ME, You YN, Ying J, Bannon SA, Lynch PM, Rodriguez-Bigas MA, et al. High prevalence of hereditary cancer syndromes in adolescents and young adults with colorectal cancer. J Clin Oncol. 2015;33(31):3544–9.
Levine O, Zbuk K. Colorectal cancer in adolescents and young adults: defining a growing threat. Pediatr Blood Cancer. 2019;66(11):e27941.
Ballinger ML, Goode DL, Ray-Coquard I, James PA, Mitchell G, Niedermayr E, et al. Monogenic and polygenic determinants of sarcoma risk: an international genetic study. Lancet Oncol. 2016;17(9):1261–71.
Chan SH, Lim WK, Ishak NDB, Li ST, Goh WL, Tan GS, et al. Germline mutations in cancer predisposition genes are frequent in sporadic sarcomas. Sci Rep. 2017;7(1):10660. https://doi.org/10.1038/s41598-017-10333-x.
Vetsch J, Wakefield CE, Doolan EL, Signorelli C, McGill B, Moore L, et al. ‘Why us?’ Causal attributions of childhood cancer survivors, survivors’ parents and community comparisons-a mixed methods analysis. Acta Oncol. 2019;58(2):209–17.
Postema FAM, Hopman SMJ, Hennekam RC, Merks JHM. Consequences of diagnosing a tumor predisposition syndrome in children with cancer: a literature review. Pediatr Blood Cancer. 2018;65(1).
Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT trial. Nat Med. 2018;24(5):628–37.
Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, et al. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin Cancer Res. 2016;22(15):3764–73.
Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 2015;5(11):1137–54.
Pilie PG, Gay CM, Byers LA, et al. PARP inhibitors: extending benefit beyond BRCA-mutant cancers. Clin Cancer Res. 2019;25(13):3759–71.
Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science (New York, NY). 2017;357(6349):409–13.
Kawakami H, Zaanan A, Sinicrope FA. Microsatellite instability testing and its role in the management of colorectal cancer. Curr Treat Options in Oncol. 2015;16(7):30.
Malkin D, Nichols KE, Schiffman JD, Plon SE, Brodeur GM. The future of surveillance in the context of cancer predisposition: through the murky looking glass. Clin Cancer Res. 2017;23(21):e133–e7.
Brodeur GM, Nichols KE, Plon SE, et al. Pediatric cancer predisposition and surveillance: an overview, and a tribute to Alfred G. Knudson Jr. Clin Cancer Res. 2017;23(11):e1–5.
Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, Druker H, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 2016;17(9):1295–305.
Murphy D, Klosky JL, Reed DR, Termuhlen AM, Shannon SV, Quinn GP. The importance of assessing priorities of reproductive health concerns among adolescent and young adult patients with cancer. Cancer. 2015;121(15):2529–36.
Friedman LC, Kramer RM. Reproductive issues for women with BRCA mutations. J Natl Cancer Inst Monogr. 2005;34:83–6.
American Society of Clinical O. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol. 2003;21(12):2397–406.
Tinat J, Bougeard G, Baert-Desurmont S, et al. 2009 version of the Chompret criteria for Li Fraumeni syndrome. J Clin Oncol. 2009;27(26):e108–9 author reply e10.
Evans DG, Harkness EF, Plaskocinska I, Wallace AJ, Clancy T, Woodward ER, et al. Pathology update to the Manchester scoring system based on testing in over 4000 families. J Med Genet. 2017;54(10):674–81.
McVeigh TP, Sundar R, Diamantis N, Kaye SB, Banerji U, Lopez JS, et al. The role of genomic profiling in adolescents and young adults (AYAs) with advanced cancer participating in phase I clinical trials. Eur J Cancer. 2018;95:20–9.
Delikurt T, Williamson GR, Anastasiadou V, Skirton H. A systematic review of factors that act as barriers to patient referral to genetic services. Eur J Hum Genet. 2015;23(6):739–45.
McVeigh TP, Donnelly D, Al Shehhi M, et al. Towards establishing consistency in triage in a tertiary specialty. Eur J Hum Genet. 2019;27(4):547–55.
Jongmans MC, Loeffen JL, Waanders E, Hoogerbrugge PM, Ligtenberg MJ, Kuiper RP, et al. Recognition of genetic predisposition in pediatric cancer patients: an easy-to-use selection tool. Eur J Med Genet. 2016;59(3):116–25.
Postema FA, Hopman SM, de Borgie CA, Hammond P, Hennekam RC, Merks JH, et al. Validation of a clinical screening instrument for tumour predisposition syndromes in patients with childhood cancer (TuPS): protocol for a prospective, observational, multicentre study. BMJ Open. 2017;7(1):e013237.
Goudie C, Coltin H, Witkowski L, Mourad S, Malkin D, Foulkes WD. The McGill Interactive Pediatric OncoGenetic Guidelines: an approach to identifying pediatric oncology patients most likely to benefit from a genetic evaluation. Pediatr Blood Cancer. 2017;64:e26441. https://doi.org/10.1002/pbc.26441.
Moss CA, Cojocaru E, Hanwell J, Ward S, Xu W, van Zyl M, et al. Multidisciplinary interventions in a specialist Drug Development Unit to improve family history documentation and onward referral of patients with advanced cancer to cancer genetics services. Eur J Cancer. 2019;114:97–106.
Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL, Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17(1):70–87.
Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015;33(31):3660–7.
Ripperger T, Bielack SS, Borkhardt A, et al. Childhood cancer predisposition syndromes-a concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology. Am J Med Genet A. 2017;173(4):1017–37.
Kuhlen M, Wieczorek D, Siebert R, et al. How I approach hereditary cancer predisposition in a child with cancer. Pediatr Blood Cancer. 2019;66(11):e27916.
Postema FAM, Hopman SMJ, Aalfs CM, Berger LPV, Bleeker FE, Dommering CJ, et al. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation. Eur J Cancer. 2017;80:48–54.
Lynch HT, Lynch PM, Lanspa SJ, et al. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76(1):1–18.
Gaal J, Stratakis CA, Carney JA, et al. SDHB immunohistochemistry: a useful tool in the diagnosis of Carney-Stratakis and Carney triad gastrointestinal stromal tumors. Mod Pathol. 2011;24(1):147–51.
Gill AJ. Use of SDHB immunohistochemistry to identify germline mutations of SDH genes. Hered Cancer Clin Pract. 2012;10(Suppl 2):A7-A.
Aimé A, Coulet F, Lefevre JH, et al. Somatic c.34G>T KRAS mutation: a new prescreening test for MUTYH-associated polyposis? Cancer Genet. 2015;208(7):390–5.
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21.
Merks JH, Ozgen HM, Koster J, Zwinderman AH, Caron HN, Hennekam RC. Prevalence and patterns of morphological abnormalities in patients with childhood cancer. JAMA. 2008;299(1):61–9.
Narod SA, Hawkins MM, Robertson CM, Stiller CA. Congenital anomalies and childhood cancer in Great Britain. Am J Hum Genet. 1997;60(3):474–85.
Miller RW. Childhood cancer and congenital defects. A study of U.S. death certificates during the period 1960-1966. Pediatr Res. 1969;3(5):389–97.
Wood ME, Kadlubek P, Pham TH, Wollins DS, Lu KH, Weitzel JN, et al. Quality of cancer family history and referral for genetic counseling and testing among oncology practices: a pilot test of quality measures as part of the American Society of Clinical Oncology Quality Oncology Practice Initiative. J Clin Oncol. 2014;32(8):824–9.
Lu KH, Wood ME, Daniels M, Burke C, Ford J, Kauff ND, et al. American Society of Clinical Oncology expert statement: collection and use of a cancer family history for oncology providers. J Clin Oncol. 2014;32(8):833–40.
Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017;19(2):249–55.
Bush LW, Bartoshesky LE, David KL, et al. Pediatric clinical exome/genome sequencing and the engagement process: encouraging active conversation with the older child and adolescent: points to consider-a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2018;20(7):692–4.
Brierley J, Larcher V. Adolescent autonomy revisited: clinicians need clearer guidance. J Med Ethics. 2016;42(8):482–5.
Lake PW, Kasting ML, Dean M, Fuzzell L, Hudson J, Carvajal R, et al. Exploring patient and provider perspectives on the intersection between fertility, genetics, and family building. Support Care Cancer. 2020. https://doi.org/10.1007/s00520-020-05315-1.
Snyder C. Evolution of cancer risk assessment and counseling related to psychological, financial and legal implications. Familial Cancer. 2016;15(3):493–6.
Bancroft EK, Saya S, Brown E, Thomas S, Taylor N, Rothwell J, et al. Psychosocial effects of whole-body MRI screening in adult high-risk pathogenic TP53 mutation carriers: a case-controlled study (SIGNIFY). J Med Genet. Published Online First: 12 November 2019. https://doi.org/10.1136/jmedgenet-2019-106407.
Lammens CR, Bleiker EM, Aaronson NK, Wagner A, Sijmons RH, Ausems MG, et al. Regular surveillance for li-Fraumeni syndrome: advice, adherence and perceived benefits. Familial Cancer. 2010;9(4):647–54.
Gulani V, Calamante F, Shellock FG, et al. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol. 2017;16(7):564–70.
Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet (London, England). 2012;380(9840):499–505.
Oliveri S, Pricolo P, Pizzoli S, et al. Investigating cancer patient acceptance of whole body MRI. Clin Imaging. 2018;52:246–51.
Anupindi SA, Bedoya MA, Lindell RB, et al. Diagnostic performance of whole-body MRI as a tool for cancer screening in children with genetic cancer-predisposing conditions. AJR Am J Roentgenol. 2015;205(2):400–8.
Jasperson KW, Kohlmann W, Gammon A, et al. Role of rapid sequence whole-body MRI screening in SDH-associated hereditary paraganglioma families. Familial Cancer. 2014;13(2):257–65.
Eshed I, Althoff CE, Hamm B, Hermann KG. Claustrophobia and premature termination of magnetic resonance imaging examinations. J Magn Reson Imaging. 2007;26(2):401–4.
Dewey M, Schink T, Dewey CF. Claustrophobia during magnetic resonance imaging: cohort study in over 55,000 patients. J Magn Reson Imaging. 2007;26(5):1322–7.
Thorpe S, Salkovskis PM, Dittner A. Claustrophobia in MRI: the role of cognitions. Magn Reson Imaging. 2008;26(8):1081–8.
Saade-Lemus S, Degnan AJ, Acord MR, Srinivasan AS, Reid JR, Servaes SE, et al. Whole-body magnetic resonance imaging of pediatric cancer predisposition syndromes: special considerations, challenges and perspective. Pediatr Radiol. 2019;49(11):1506–15.
Greer MC. Imaging of cancer predisposition syndromes. Pediatr Radiol. 2018;48(9):1364–75.
Stoll K, Kubendran S, Cohen SA. The past, present and future of service delivery in genetic counseling: keeping up in the era of precision medicine. Am J Med Genet C: Semin Med Genet. 2018;178(1):24–37.
Lynch SA, Borg I. Wide disparity of clinical genetics services and EU rare disease research funding across Europe. J Community Genet. 2016;7(2):119–26.
McCuaig JM, Armel SR, Care M, et al. Next-generation service delivery: a scoping review of patient outcomes associated with alternative models of genetic counseling and genetic testing for hereditary cancer. Cancers (Basel). 2018;10(11):435. https://doi.org/10.3390/cancers10110435.
Stearnes G, Nichols CB, Schofield L, O’Sullivan S, Pachter N, Cohen PA. Uptake of testing for germline BRCA mutations in patients with non-mucinous epithelial ovarian cancers in Western Australia: a comparison of different genetic counseling methods. Int J Gynecol Cancer. 2019;29(6):1038–42.
NHS Genomic Medicine Service [Available from: https://www.england.nhs.uk/genomics/nhs-genomic-med-service/.
Saya S, Killick E, Thomas S, Taylor N, Bancroft EK, Rothwell J, et al. Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls. Familial Cancer. 2017;16(3):433–40.
Duncan RE, Gillam L, Savulescu J, et al. “You’re one of us now”: young people describe their experiences of predictive genetic testing for Huntington disease (HD) and familial adenomatous polyposis (FAP). Am J Med Genet C: Semin Med Genet. 2008;148C(1):47–55.
Vetsch J, Wakefield CE, Warby M, Tucker K, Patterson P, McGill B, et al. Cancer-related genetic testing and personalized medicine for adolescents: a narrative review of impact and understanding. J Adolesc Young Adult Oncol. 2018;7(3):259–62.
Mand C, Gillam L, Duncan RE, Delatycki MB. “It was the missing piece”: adolescent experiences of predictive genetic testing for adult-onset conditions. Genet Med. 2013;15(8):643–9.
Conflict of Interest
The authors declare that they have no conflicts of interest associated with this manuscript.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Cancer Genomics
About this article
Cite this article
Cullinan, N., Capra, M. & McVeigh, T.P. Genetic Testing for Cancer Predisposition Syndromes in Adolescents and Young Adults (AYAs). Curr Genet Med Rep 8, 61–71 (2020). https://doi.org/10.1007/s40142-020-00187-7
- Cancer predisposition syndromes
- Adolescent and young adult
- Hereditary cancer