Abstract
Presymptomatic genetic testing in childhood for adult onset conditions is generally discouraged as it does not directly benefit the child and removes their autonomy. In certain cancer prone conditions such as Familial Adenomatous Polyposis and Von Hippel Lindau disease there are risks of disease in childhood and benefit to children not inheriting a mutation in being able to forego unpleasant screening tests. Li–Fraumeni syndrome caused by constitutional TP53 mutations there are also implications in childhood with a risk of around 20% of a childhood malignancy. However, as yet no evidence based surveillance programme has been identified. We describe our experience of childhood testing for four children in two Li–Fraumeni families caused by TP53 mutations.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Li FP, Fraumeni JF (1969) Jr Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 71:747–752
Lynch T, Krush AJ, Harlan WL, Sharp EA (1973) Association of soft tissue sarcoma, leukemia and brain tumors in families affected with breast cancer. Am Surg 39:199–206
Pearson AJ, Craft AW, Ratcliffe JM et al (1982) Two families with the Li–Fraumeni cancer family syndrome. J Med Genet 19:362–365. doi:10.1136/jmg.19.5.362
Li FP, Fraumeni JF Jr (1982) Prospective study of a family cancer syndrome. JAMA 247:2692–2694. doi:10.1001/jama.247.19.2692
Birch JM, Hartley AL, Marsden HB et al (1984) Excess risk of breast cancer in the mothers of children with soft tissue sarcomas. Br J Cancer 49:325–331
Birch JM, Hartley L, Blair V et al (1990) Cancer in the families of children with soft tissue sarcoma. Cancer 66:2239–2248. doi:10.1002/1097-0142(19901115)66:10<2239::AID-CNCR2820661034>3.0.CO;2-Q
Birch JM, Hartley AL, Blair V et al (1990) Identification of factors associated with high breast cancer risk in the mothers of children with soft tissue sarcoma. J Clin Oncol 8:583–590
Strong LC, Stine M, Norsted TL (1987) Cancer in survivors of childhood soft tissue sarcoma and their relatives. J Natl Cancer Inst 79:1213–1220
Malkin D, Li F, Strong LC et al (1990) Germline p53 mutations in a familial syndrome of breast cancer, sarcomas and other neoplasms. Science 250:1233–1238. doi:10.1126/science.1978757
Srivastava S, Zou Z, Pirollo K et al (1990) Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li–Fraumeni syndrome. Nature 348:747–749. doi:10.1038/348747a0
Birch JM, Hartley AL, Tricker J et al (1994) Prevalence and diversity of constitutional Mutations in the p53 Gene among 21 Li–Fraumeni Families. Cancer Res 54:1298–1304
Frebourg T, Barbier N, Yan Y-X et al (1995) Germ-line p53 Mutations in 15 Families with Li–Fraumeni Syndrome. Am J Hum Genet 56:608–615
Chompret A, Brugières L, Ronsin M (2000) Gardes M et alp53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer 82:1932–1937. doi:10.1054/bjoc.2000.1167
Varley JM, McGown G, Thorncroft M et al (1997) Germ-line mutations of TP53 in Li–Fraumeni families: an extended study of 39 families. Cancer Res 57:3245–3252
Birch JM, Blair V, Kelsey AM et al (1998) Cancer phenotype correlates with constitutional TP53 genotype in families with the Li–Fraumeni syndrome. Oncogene 17:1061–1068. doi:10.1038/sj.onc.1202033
Lalloo F, Varley J, Ellis D, O’Dair L, Pharoah P (2003) Evans DGR and the early onset breast cancer study Group. Family history is predictive of pathogenic mutations in BRCA1, BRCA2 and TP53 with high penetrance in a population based study of very early onset breast cancer. Lancet 361:1101–1102. doi:10.1016/S0140-6736(03)12856-5
Olivier M, Goldgar DE, Sodha N, Ohgaki H, Kleihues P, Hainaut P, Eeles RA (2003) Li–Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res 63(20):6643–6650
Moule RN, Jhavar SG, Eeles RA (2006) Genotype phenotype correlation in Li–Fraumeni syndrome kindreds and its implications for management. Fam Cancer 5(2):129–133. doi:10.1007/s10689-005-4522-8
Birch JM, Alston RD, McNally RJQ et al (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20:4621–4628. doi:10.1038/sj.onc.1204621
Varley JM, Evans DGR, Birch JM (1997) Li–Fraumeni syndrome—a molecular and clinical review. Br J Cancer 76(1):1–14
Evans DGR, Morrison P (2004) The ethical and insurance issues in testing for cancer -predisposition genes. In: Eeles R, Ponder B, Easton D, Eng C, Horwich A (eds) Genetic predisposition to cancer, 2nd edn. Chapman and Hall, London, pp 414–423
Evans DGR, Maher ER, Macleod R, Davies DR, Craufurd D (1997) Uptake of genetic testing for cancer predisposition. J Med Genet 34:746–748. doi:10.1136/jmg.34.9.746
Eeles RA (1993) Predictive testing for germline mutations in the p53 gene: are all the questions answered? Eur J Cancer 29A(10):1361–1365. doi:10.1016/0959-8049(93)90001-V
Lalloo F, Baildam A, Brain A, Hopwood P, Howell A, Evans DGR (2000) Preventative mastectomy for women at high risk of breast cancer. Eur J Surg Oncol 26:711–713. doi:10.1053/ejso.2000.0986
Masciari S, Van den Abbeele AD, Diller LR, Rastarhuyeva I, Yap J, Schneider K, Digianni L, Li FP, Fraumeni JF Jr, Syngal S, Garber JE (2008) F18-fluorodeoxyglucose-positron emission tomography/computed tomography screening in Li–Fraumeni syndrome. JAMA 299(11):1315–1319. doi:10.1001/jama.299.11.1315
Evans DGR, Birch JM, Ramsden RT, Moffat D, Baser ME (2006) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour-prone syndromes. J Med Genet 43(4):289–294. doi:10.1136/jmg.2005.036319
Michie S, Bobrow M, Marteau TM (2001) Predictive genetic testing in children and adults: a study of emotional impact. J Med Genet 38(8):519–526. doi:10.1136/jmg.38.8.519
Peterson SK, Pentz RD, Blanco AM, Ward PA, Watts BG, Marani SK, James LC, Strong LC (2006) Evaluation of a decision aid for families considering p53 genetic counseling and testing. Genet Med 8(4):226–233. doi:10.1097/01.gim.0000214632.52958.01
Schneider KA, Patenaude AF, Garber JE (1995) Testing for cancer genes: decisions, decisions. Nat Med 1(4):302–303. doi:10.1038/nm0495-302
Acknowledgments
We acknowledge the support of the Biomedical Research Centre at Central Manchester Foundation Trust. We acknowledge NHS support to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Evans, D.G., Lunt, P., Clancy, T. et al. Childhood predictive genetic testing for Li–Fraumeni syndrome. Familial Cancer 9, 65–69 (2010). https://doi.org/10.1007/s10689-009-9245-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-009-9245-9