Advertisement

Preventive and Predictive Genetics: A perspective

  • Godfrey GrechEmail author
  • Christian Scerri
  • Jeanesse Scerri
  • Tomris Cesuroglu
Chapter
Part of the Advances in Predictive, Preventive and Personalised Medicine book series (APPPM, volume 9)

Abstract

Public Health practices focus on the implementation of programmes for health improvement and disease prevention (Khoury et al., Am J Prev Med 40(4):486–493, 2011). Public health initiatives in disease were initially targeted to prevent infectious diseases. Partly due to the availability of vaccines and anti-microbial therapy and partly due to better standard of living, the world is free of diseases such as small pox, almost free of polio and the prevalence of infections such as malaria and HIV is steadily on the decline. This has meant that the human race is living longer with the result that non-communicable diseases have become a global public health priority. Preventing non-communicable diseases is a more logical approach than treating them, even more so when modifiable, common lifestyle risk factors share a role in the onset and progression of the disease. Preventive genetics plays a crucial role in the identification of subjects at risk at a very early age, which would thus give public health officials the necessary time to take appropriate action.

Genetic tests can be classified into carrier, diagnostic and predictive testing. In carrier testing, the tests are directed towards the identification of carriers of autosomal recessive or X-linked genetic disorders to prevent disease. Preventive genetics can be defined as using genetics for the prevention of a future disease that has a genetic component either in the individual tested or in future offspring. Diagnostic testing is the process that identifies the current disease status of the subject and includes, among others, prenatal and newborn screening. The implementation of screening programmes allow the detection of genetic disorders at an early stage, so as to prevent these conditions or their serious consequences. Predictive testing determines whether a subject with a positive history but no symptoms of the disease, is at risk of developing the disorder at a future date. In this chapter, we will discuss the application of genetic screening tests to monogenic disorders and complex disorders with monogenic subsets, in view of the current practices. The multifactorial aetiology of complex disorders involves multiple gene effects and gene-lifestyle interactions that cannot be singled out to give a strong predictive value. However, a subset of the complex disorders are caused by highly penetrant genetic mutations. Hence, in this chapter we shall also address predisposing syndromes with high predictive value. In addition, the need of biobanks will be discussed.

Keywords

Public health genomics Preventive genetics Predictive genetics Screening programmes Monogenic disorders Monogenic syndromes Biobanks 

References

  1. 1.
    Khoury MJ, Bowen MS, Burke W, Coates RJ, Dowling NF, Evans JP, Reyes M, St Pierre J (2011) Current priorities for public health practice in addressing the role of human genomics in improving population health. Am J Prev Med 40(4):486–493. doi:10.1016/j.amepre.2010.12.009PubMedCrossRefGoogle Scholar
  2. 2.
    Morabia A, Zhang FF (2004) History of medical screening: from concepts to action. Postgrad Med J 80(946):463–469. doi:10.1136/pgmj.2003.018226PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Wilson JM, Jungner YG (1968) Principles and practice of mass screening for disease. Bol Oficina Sanit Panam 65 (4):281–393PubMedGoogle Scholar
  4. 4.
    Andermann A, Blancquaert I, Beauchamp S, Déry V (2008) Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years. Bull World Health Organ 86(4):241–320CrossRefGoogle Scholar
  5. 5.
    Becker F, van El CG, Ibarreta D, Zika E, Hogarth S, Borry P, Cambon-Thomsen A, Cassiman JJ, Evers-Kiebooms G, Hodgson S, Janssens AC, Kaariainen H, Krawczak M, Kristoffersson U, Lubinski J, Patch C, Penchaszadeh VB, Read A, Rogowski W, Sequeiros J, Tranebjaerg L, van Langen IM, Wallace H, Zimmern R, Schmidtke J, Cornel MC (2011) Genetic testing and common disorders in a public health framework: how to assess relevance and possibilities. Eur J Hum Genet 19(Suppl 1):S6–S44. doi:10.1038/ejhg.2010.249Google Scholar
  6. 6.
    IRDiRC (2012) International rare diseases research. http://www.irdirc.org. Accessed 22 Apr 2014
  7. 7.
    Gilissen C, Hoischen A, Brunner HG, Veltman JA (2011) Unlocking Mendelian disease using exome sequencing. Genome Biol 12(9). doi:10.1186/gb-2011-12-9-228Google Scholar
  8. 8.
    Guthrie R, Susi A (1963) A simple phenylalanine method for detecting Phenylketonuria in large populations of newborn infants. Pediatrics 32:338–343PubMedGoogle Scholar
  9. 9.
    Ozben T (2013) Expanded newborn screening and confirmatory follow-up testing for inborn errors of metabolism detected by tandem mass spectrometry. Clin Chem Lab Med 51(1):157–176. doi:10.1515/cclm-2012-0472PubMedCrossRefGoogle Scholar
  10. 10.
    O’Neill CA, Eisensmith RC, Croke DT, Naughten ER, Cahalane SF, Woo SL (1994) Molecular analysis of PKU in Ireland. Acta Paediatr Suppl 407:43–44PubMedCrossRefGoogle Scholar
  11. 11.
    Guldberg P, Henriksen KF, Sipila I, Guttler F, de la Chapelle A (1995) Phenylketonuria in a low incidence population: molecular characterisation of mutations in Finland. J Med Genet 32(12):976–978PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Oerton J, Khalid JM, Besley G, Dalton RN, Downing M, Green A, Henderson M, Krywawych S, Leonard J, Andresen BS, Dezateux C (2011) Newborn screening for medium chain acyl-CoA dehydrogenase deficiency in England: prevalence, predictive value and test validity based on 1.5 million screened babies. J Med Screen 18(4):173–181. doi:10.1258/jms.2011.011086PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Wilcken B, Leung KC, Hammond J, Kamath R, Leonard JV (1993) Pregnancy and fetal long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency. Lancet 341(8842):407–408. doi:10.1016/0140-6736(93)92993-4PubMedCrossRefGoogle Scholar
  14. 14.
    Leonard JV, Dezateux C (2009) Newborn screening for medium chain acyl CoA dehydrogenase deficiency. Arch Dis Child 94(3):235–238. doi:10.1136/adc.2007.134957PubMedCrossRefGoogle Scholar
  15. 15.
    Yap S, Naughten E (1998) Homocystinuria due to cystathionine beta-synthase deficiency in Ireland: 25 years’ experience of a newborn screened and treated population with reference to clinical outcome and biochemical control. J Inherit Metab Dis 21(7):738–747PubMedCrossRefGoogle Scholar
  16. 16.
    Carleton SM, Peck DS, Grasela J, Dietiker KL, Phillips CL (2010) DNA carrier testing and newborn screening for maple syrup urine disease in Old Order Mennonite communities. Genet Test Mol Biomarkers 14(2):205–208. doi:10.1089/gtmb.2009.0107PubMedCrossRefGoogle Scholar
  17. 17.
    Edelmann L, Wasserstein MP, Kornreich R, Sansaricq C, Snyderman SE, Diaz GA (2001) Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. Am J Hum Genet 69(4):863–868. doi:10.1086/323677PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Puffenberger EG (2003) Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. Am J Med Genet C Semin Med Genet 121C(1):18–31. doi:10.1002/ajmg.c.20003CrossRefGoogle Scholar
  19. 19.
    Kolker S, Christensen E, Leonard JV, Greenberg CR, Burlina AB, Burlina AP, Dixon M, Duran M, Goodman SI, Koeller DM, Muller E, Naughten ER, Neumaier-Probst E, Okun JG, Kyllerman M, Surtees RA, Wilcken B, Hoffmann GF, Burgard P (2007) Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I). J Inherit Metab Dis 30(1):5–22. doi:10.1007/s10545-006-0451-4PubMedCrossRefGoogle Scholar
  20. 20.
    Collins FS (1992) Cystic fibrosis: molecular biology and therapeutic implications. Science 256(5058):774–779. doi:10.1126/science.256.5058.774PubMedCrossRefGoogle Scholar
  21. 21.
    Massie J, Delatycki MB (2013) Cystic fibrosis carrier screening. Paediatric Respir Rev 14(4):270–275. doi:10.1016/j.prrv.2012.12.002Google Scholar
  22. 22.
    Barrett PM, Alagely A, Topol EJ (2012) Cystic fibrosis in an era of genomically guided therapy. Human Mol Genet 21(R1):R66–R71. doi:10.1093/hmg/dds345Google Scholar
  23. 23.
    O’Sullivan BP, Freedman SD (2009) Cystic fibrosis. The Lancet 373(9678):1891–1904. doi:10.1016/s0140-6736(09)60327-5CrossRefGoogle Scholar
  24. 24.
    Hurt K, Bilton D (2012) Cystic fibrosis. Medicine 40(5):273–276. doi:10.1016/j.mpmed.2012.02.006CrossRefGoogle Scholar
  25. 25.
    Dodge JA, Lewis PA, Stanton M, Wilsher J (2007) Cystic fibrosis mortality and survival in the UK: 1947–2003. Eur Respir J 29(3):522–526. doi:10.1183/09031936.00099506PubMedCrossRefGoogle Scholar
  26. 26.
    Grody WW, Cutting GR, Klinger KW, Richards CS, Watson MS, Desnick RJ, Subcommittee on Cystic Fibrosis screening AoGSCAACoMG (2001) Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med 3(2):149–154. doi:10.109700125817-200103000-00010PubMedCrossRefGoogle Scholar
  27. 27.
    Watson MS, Cutting GR, Desnick RJ, Driscoll DA, Klinger K, Mennuti M, Palomaki GE, Popovich BW, Pratt VM, Rohlfs EM, Strom CM, Richards CS, Witt DR, Grody WW (2004) Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med 6(5):387–391. doi:10.1097/01.gim.0000139506.11694.7cPubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM, Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett N, Dong Q, Zha J, Stone AJ, Olson ER, Ordonez CL, Campbell PW, Ashlock MA, Ramsey BW (2010) Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med 363(21):1991–2003. doi:10.1056/NEJMoa0909825PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Sermet-Gaudelus I, Boeck KD, Casimir GJ, Vermeulen F, Leal T, Mogenet A, Roussel D, Fritsch J, Hanssens L, Hirawat S, Miller NL, Constantine S, Reha A, Ajayi T, Elfring GL, Miller LL (2010) Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis. Am J Respir Crit Care Med 182(10):1262–1272. doi:10.1164/rccm.201001-0137OCPubMedCrossRefGoogle Scholar
  30. 30.
    Roberts DJ, Williams TN (2003) Haemoglobinopathies and resistance to malaria. Redox Rep 8(5):304–310. doi:10.1179/135100003225002998PubMedCrossRefGoogle Scholar
  31. 31.
    Galanello R, Origa R (2010) Beta-thalassemia. Orphanet J Rare Dis 5:11. doi:10.1186/1750-1172-5-11Google Scholar
  32. 32.
    Limdi JK, Crampton JR (2004) Hereditary haemochromatosis. QJM 97(6):315–324. doi:10.1093/qjmed/hch065PubMedCrossRefGoogle Scholar
  33. 33.
    Hanson EH, Imperatore G, Burke W (2001) HFE gene and hereditary hemochromatosis: A HuGE review. Am J Epidemiol 154(3):193–206. doi:10.1093/aje/154.3.193PubMedCrossRefGoogle Scholar
  34. 34.
    Merryweather-Clarke AT, Pointon JJ, Jouanolle AM, Rochette J, Robson KJH (2000) Geography of HFE C282Y and H63D Mutations. Genetic Test 4(2):183–198. doi:10.1089/10906570050114902CrossRefGoogle Scholar
  35. 35.
    Niederau C, Fischer R, Pürschel A, Stremmel W, Häussinger D, Strohmeyer G (1996) Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110(4):1107–1119PubMedCrossRefGoogle Scholar
  36. 36.
    Austin MA, Hutter CM, Zimmern RL, Humphries SE (2004) Familial hypercholesterolemia and coronary heart disease: A HuGE association review. Am J Epidemiol 160(5):421–429. doi:10.1093/aje/kwh237PubMedCrossRefGoogle Scholar
  37. 37.
    Varret M, Abifadel M, Rabès JP, Boileau C (2008) Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet 73(1):1–13. doi:10.1111/j.1399-0004.2007.00915.xPubMedCrossRefGoogle Scholar
  38. 38.
    Ned RM, Sijbrands EJG (2011) Cascade screening for familial hypercholesterolemia (FH). PLoS Curr 3:RRN1238. doi:10.1371/currents.RRN1238Google Scholar
  39. 39.
    Neil A, Cooper J, Betteridge J, Capps N, McDowell I, Durrington P, Seed M, Humphries SE (2008) Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur Heart J 29(21):2625–2633. doi:10.1093/eurheartj/ehn422PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Williams RR, Hamilton-Craig I, Kostner GM, Hegele RA, Hayden MR, Pimstone SN, Faergeman O, Schuster H, Steinhagen-Thiessen E, Beisiegel U, Keller C, Czeizel AE, Leitersdore E, Kastelein JC, Defesche JJP, Ose L, Leren TP, Seftel HC, Raal FJ, Marais AD, Eriksson M, Keller U, Miserez AR, Jeck T, Betterridge DJ, Humphries SE, Day INM, Kwiterovich PO, Lees RS, Stein E, Illingworth R, Kane J, Boulyjenkov V (1996) MED-PED: An integrated genetic strategy for preventing early deaths. In: Dr KBP, Dr VB, Dr YC (eds) Genetic approaches to noncommunicable diseases. Springer, Berlin, pp 35–45Google Scholar
  41. 41.
    Williams RR, Hunt SC, Schumacher MC, Hegele RA, Leppert MF, Ludwig EH, Hopkins PN (1993) Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol 72(2):171–176PubMedCrossRefGoogle Scholar
  42. 42.
    Bertolini S, Cantafora A, Averna M, Cortese C, Motti C, Martini S, Pes G, Postiglione A, Stefanutti C, Blotta I, Pisciotta L, Rolleri M, Langheim S, Ghisellini M, Rabbone I, Calandra S (2000) Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype. Arterioscler Thromb Vasc Biol 20(9):e41–e52. doi:10.1161/01.ATV.20.9.e41Google Scholar
  43. 43.
    Scientific Steering Committee on behalf of the Simon Broome Register Group (1991) Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ 303(6807):893–896Google Scholar
  44. 44.
    World Health O (1999) Familial hypercholesterolaemia: report of a second WHO consultation. WHO, GenevaGoogle Scholar
  45. 45.
    Javaher P, Nyoungui E, Kaariainen H, Kristoffersson U, Nippert I, Sequeiros J, Schmidtke J (2010) Genetic screening in Europe. Public Health Gen 13(7–8):524–537. doi:10.1159/000294998CrossRefGoogle Scholar
  46. 46.
    Rastogi MV, LaFranchi SH (2010) Congenital hypothyroidism. Orphanet J Rare Dis 5:17. doi:10.1186/1750–1172-5-17PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Comeau AM, Accurso FJ, White TB, Campbell PW 3rd, Hoffman G, Parad RB, Wilfond BS, Rosenfeld M, Sontag MK, Massie J, Farrell PM, O’Sullivan BP (2007) Guidelines for implementation of cystic fibrosis newborn screening programs: Cystic Fibrosis Foundation workshop report. Pediatrics 119(2):e495–518. doi:10.1542/peds.2006-1993CrossRefGoogle Scholar
  48. 48.
    Loeber JG, Burgard P, Cornel MC, Rigter T, Weinreich SS, Rupp K, Hoffmann GF, Vittozzi L (2012) Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1. From blood spot to screening result. J Inherit Metab Dis 35(4):603–611. doi:10.1007/s10545-012-9483-0PubMedCrossRefGoogle Scholar
  49. 49.
    Godard B, ten Kate L, Evers-Kiebooms G, Aymé S (2003) Population genetic screening programmes: principles, techniques, practices, and policies. Eur J Hum Genet 11(S2):S49–S87. doi:10.1038/sj.ejhg.5201113Google Scholar
  50. 50.
    Gemeinsamer Bundesausschuss (G-BA) Mandate of the Federal Joint Committee. (2014) http://www.english.g-ba.de/special-topics/prevention/mandate/. Accessed 05 June 2014
  51. 51.
    UK National Screening Committee (2013) Programme appraisal criteria—Criteria for appraising the viability, effectiveness and appropriateness of a screening programme. http://www.screening.nhs.uk/criteria. Accessed 05 Jun 2014
  52. 52.
    Sanderman LK (2011) Newborn screening in Europe: lessons learned from tandem mass spectrometry in Germany and the UK. (Master of Science) Maastricht University, MaastrichtGoogle Scholar
  53. 53.
    Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458(7239):719–724PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Wright C, Burton H, Hall A, Moorthie S, Pokorska-Bocci A, Sagoo G, Sanderson S, Skinner R (2011) Next steps in the sequence. The implications of whole genome sequencing for health in the UK. PHG Foundation, CambridgeGoogle Scholar
  55. 55.
    Schröder P, Zimmern R (2007) PHGEN Working Group 2– The status of genetic information and genetic testing. Consequences for Public Health Genomics and the Public Health Genomics European Network (PHGEN). http://ec.europa.eu/health/screening_genetics/genomics/index_en.htm, Accessed 05 Jun 2014
  56. 56.
    Burke W, Burton H, Hall AE, Karmali M, Khoury MJ, Knoppers B, Meslin EM, Stanley F, Wright CF, Zimmern RL (2010) Extending the reach of public health genomics: what should be the agenda for public health in an era of genome-based and “personalized” medicine? Genet Med 12(12):785–791PubMedCrossRefGoogle Scholar
  57. 57.
    EAPM (2013) Innovation and patient access to personalised medicine—Report from Irish Presidency Conference March 20th/21st 2013. http://euapm.eu/wp-content/uploads/2012/07/EAPM-REPORT-on-Innovation-and-Patient-Access-to-Personalised-Medicine.pdf. ­Accessed 05 Jun 2014
  58. 58.
    Wellcome Trust (2013) Impact of the draft European Data Protection Regulation and proposed amendments from the rapporteur of the LIBE committee on scientific research. http://www.wellcome.ac.uk/stellent/groups/corporatesite/@policy_communications/documents/web_document/wtvm054713.pdf. Accessed 16 Nov 2013
  59. 59.
    Ploem MC, Essink-Bot ML, Stronks K (2013) Proposed EU data protection regulation is a threat to medical research. BMJ 346:f3534. doi:10.1136/bmj.f3534Google Scholar
  60. 60.
    Brice P (2013) EU legal amendments threaten genomic medicine and research. PHG Foundation. http://www.phgfoundation.org/news/ 14842 /. Accessed 16 Nov 2013
  61. 61.
    Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O’Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 15(7):565–574. doi:10.1038/gim.2013.73PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56(1):265–271PubMedCentralPubMedGoogle Scholar
  63. 63.
    Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Zelada-Hedman M, the Breast Cancer Linkage Consortium (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62(3):676–689. doi:10.1086/301749PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Lynch HT, Smyrk T, Lynch JF (1998) Molecular genetics and clinical-pathology features of hereditary nonpolyposis colorectal carcinoma (Lynch syndrome): historical journey from pedigree anecdote to molecular genetic confirmation. Oncology 55(2):103–108.PubMedCrossRefGoogle Scholar
  65. 65.
    Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276(5321):2045–2047PubMedCrossRefGoogle Scholar
  66. 66.
    Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10(8):789–799. doi:10.1038/nm1087PubMedCrossRefGoogle Scholar
  67. 67.
    Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, Easton DF, Stratton MR (2007) PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39(2):165–167. doi:10.1038/ng1959PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, Chagtai T, Jayatilake H, Ahmed M, Spanova K, North B, McGuffog L, Evans DG, Eccles D, Easton DF, Stratton MR, Rahman N (2006) Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 38(11):1239–1241. doi:10.1038/ng1902PubMedCrossRefGoogle Scholar
  69. 69.
    Somyajit K, Subramanya S, Nagaraju G (2010) RAD51C: a novel cancer susceptibility gene is linked to Fanconi anemia and breast cancer. Carcinogenesis 31(12):2031–2038. doi:10.1093/carcin/bgq210PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Lensch MW, Tischkowitz M, Christianson TA, Reifsteck CA, Speckhart SA, Jakobs PM, O'Dwyer ME, Olson SB, Le Beau MM, Hodgson SV, Mathew CG, Larson RA, Bagby GC, Jr. (2003) Acquired FANCA dysfunction and cytogenetic instability in adult acute myelogenous leukemia. Blood 102(1):7–16. doi:10.1182/blood-2002–09-2781PubMedCrossRefGoogle Scholar
  71. 71.
    Garber JE, Offit K (2005) Hereditary cancer predisposition syndromes. J Clin Oncol 23(2):276–292. doi:10.1200/JCO.2005.10.042PubMedCrossRefGoogle Scholar
  72. 72.
    McBride KA, Ballinger ML, Killick E, Kirk J, Tattersall MH, Eeles RA, Thomas DM, Mitchell G (2014) Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nat Rev Clin Oncol. doi:10.1038/nrclinonc.2014.41Google Scholar
  73. 73.
    Francke U (1976) Retinoblastoma and chromosome 13. Cytogenet Cell Genet 16(1–5):131–134PubMedCrossRefGoogle Scholar
  74. 74.
    Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, Crabtree JS, Wang Y, Roe BA, Weisemann J, Boguski MS, Agarwal SK, Kester MB, Kim YS, Heppner C, Dong Q, Spiegel AM, Burns AL, Marx SJ (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276(5311):404–407PubMedCrossRefGoogle Scholar
  75. 75.
    Gnarra JR, Duan DR, Weng Y, Humphrey JS, Chen DY, Lee S, Pause A, Dudley CF, Latif F, Kuzmin I, Schmidt L, Duh FM, Stackhouse T, Chen F, Kishida T, Wei MH, Lerman MI, Zbar B, Klausner RD, Linehan WM (1996) Molecular cloning of the von Hippel-Lindau tumor suppressor gene and its role in renal carcinoma. Biochim Biophys Acta 1242(3):201–210PubMedGoogle Scholar
  76. 76.
    Hirshfield KM, Rebbeck TR, Levine AJ (2010) Germline mutations and polymorphisms in the origins of cancers in women. J Oncol 2010:1–11. doi:10.1155/2010/297671CrossRefGoogle Scholar
  77. 77.
    Samoha S, Arber N (2005) Cyclooxygenase-2 inhibition prevents colorectal cancer: from the bench to the bed side. Oncology 69(Suppl 1):33–37. doi:10.1159/000086630PubMedCrossRefGoogle Scholar
  78. 78.
    Lynch PM (2007) Prevention of colorectal cancer in high-risk populations: the increasing role for endoscopy and chemoprevention in FAP and HNPCC. Digestion 76(1):68–76. doi:10.1159/000108395PubMedCrossRefGoogle Scholar
  79. 79.
    Rozen P, Samuel Z, Rabau M, Goldman G, Shomrat R, Legum C, Orr-Urtreger A (2001) Familial adenomatous polyposis at the Tel Aviv Medical Center: demographic and clinical features. Fam Cancer 1(2):75–82PubMedCrossRefGoogle Scholar
  80. 80.
    Malkin D, Li FP, Strong LC, Fraumeni JF, Jr., Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, Friend SH (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250(4985):1233–1238PubMedCrossRefGoogle Scholar
  81. 81.
    Gonzalez KD, Noltner KA, Buzin CH, Gu D, Wen-Fong CY, Nguyen VQ, Han JH, Lowstuter K, Longmate J, Sommer SS, Weitzel JN (2009) Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol 27(8):1250–1256. doi:10.1200/jco.2008.16.6959PubMedCrossRefGoogle Scholar
  82. 82.
    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):6643–6650PubMedGoogle Scholar
  83. 83.
    Lalloo F, Varley J, Ellis D, Moran A, O’Dair L, Pharoah P, Evans DG (2003) Prediction of pathogenic mutations in patients with early-onset breast cancer by family history. Lancet 361(9363):1101–1102. doi:10.1016/S0140-6736(03)12856-5PubMedCrossRefGoogle Scholar
  84. 84.
    Li FP, Fraumeni JF, Jr., Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48(18):5358–5362PubMedGoogle Scholar
  85. 85.
    Chompret A, Abel A, Stoppa-Lyonnet D, Brugieres L, Pages S, Feunteun J, Bonaiti-Pellie C (2001) Sensitivity and predictive value of criteria for p53 germline mutation screening. J Med Genet 38(1):43–47PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Hwang SJ, Lozano G, Amos CI, Strong LC (2003) Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk. Am J Hum Genet 72(4):975–983. doi:10.1086/374567PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Farooq A, Walker LJ, Bowling J, Audisio RA (2010) Cowden syndrome. Cancer Treat Rev 36(8):577–583. doi:10.1016/j.ctrv.2010.04.002PubMedCrossRefGoogle Scholar
  88. 88.
    Hobert JA, Eng C (2009) PTEN hamartoma tumor syndrome: an overview. Genet Med 11(10):687–694. doi:10.1097/GIM.0b013e3181ac9aeaPubMedCrossRefGoogle Scholar
  89. 89.
    Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, Parsons R (1997) Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16(1):64–67. doi:10.1038/ng0597-64PubMedCrossRefGoogle Scholar
  90. 90.
    Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275(5308):1943–1947PubMedCrossRefGoogle Scholar
  91. 91.
    Scheper MA, Nikitakis NG, Sarlani E, Sauk JJ, Meiller TF (2006) Cowden syndrome: report of a case with immunohistochemical analysis and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101(5):625–631. doi:10.1016/j.tripleo.2005.06.026PubMedCrossRefGoogle Scholar
  92. 92.
    Gorlin RJ, Cohen MM, Jr., Condon LM, Burke BA (1992) Bannayan-Riley-Ruvalcaba syndrome. Am J Med Genet 44(3):307–314. doi:10.1002/ajmg.1320440309PubMedCrossRefGoogle Scholar
  93. 93.
    Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C (2012) Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 18(2):400–407. doi:10.1158/1078-0432.CCR-11-2283PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Vasen HF, Boland CR (2005) Progress in genetic testing, classification, and identification of Lynch syndrome. JAMA 293(16):2028–2030. doi:10.1001/jama.293.16.2028PubMedCrossRefGoogle Scholar
  95. 95.
    Bonadona V, Bonaiti B, Olschwang S, Grandjouan S, Huiart L, Longy M, Guimbaud R, Buecher B, Bignon YJ, Caron O, Colas C, Nogues C, Lejeune-Dumoulin S, Olivier-Faivre L, Polycarpe-Osaer F, Nguyen TD, Desseigne F, Saurin JC, Berthet P, Leroux D, Duffour J, Manouvrier S, Frebourg T, Sobol H, Lasset C, Bonaiti-Pellie C (2011) Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 305(22):2304–2310. doi:10.1001/jama.2011.743PubMedCrossRefGoogle Scholar
  96. 96.
    Vasen HF, Watson P, Mecklin JP, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116(6):1453–1456PubMedCrossRefGoogle Scholar
  97. 97.
    Boland CR, Goel A (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138 (6):2073–2087 e2073. doi:10.1053/j.gastro.2009.12.064PubMedCentralPubMedCrossRefGoogle Scholar
  98. 98.
    Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomaki P, Mecklin JP, Jarvinen HJ (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81(2):214–218. doi:10.1002/(SICI)1097-0215(19990412)81:2<214::AID-IJC8>3.0.CO;2-LGoogle Scholar
  99. 99.
    Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Muller O, Back W, Zimmer M (1998) Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18(1):38–43. doi:10.1038/ng0198-38PubMedCrossRefGoogle Scholar
  100. 100.
    Tomlinson IP, Houlston RS (1997) Peutz-Jeghers syndrome. J Med Genet 34(12):1007–1011PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, Cruz-Correa M, Offerhaus JA (2000) Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119(6):1447–1453. doi:10.1053/gast.2000.20228PubMedCrossRefGoogle Scholar
  102. 102.
    Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767. doi:10.1016/0092-8674(90)90186-IPubMedCrossRefGoogle Scholar
  103. 103.
    Gruber SB, Entius MM, Petersen GM, Laken SJ, Longo PA, Boyer R, Levin AM, Mujumdar UJ, Trent JM, Kinzler KW, Vogelstein B, Hamilton SR, Polymeropoulos MH, Offerhaus GJ, Giardiello FM (1998) Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome. Cancer Res 58(23):5267–5270PubMedGoogle Scholar
  104. 104.
    Sanchez-Cespedes M, Parrella P, Esteller M, Nomoto S, Trink B, Engles JM, Westra WH, Herman JG, Sidransky D (2002) Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res 62(13):3659–3662PubMedGoogle Scholar
  105. 105.
    Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, Keller JJ, Westerman AM, Scott RJ, Lim W, Trimbath JD, Giardiello FM, Gruber SB, Offerhaus GJ, de Rooij FW, Wilson JH, Hansmann A, Moslein G, Royer-Pokora B, Vogel T, Phillips RK, Spigelman AD, Houlston RS (2006) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12(10):3209–3215. doi:10.1158/1078-0432.CCR-06-0083PubMedCrossRefGoogle Scholar
  106. 106.
    Khoury MJ, Feero WG, Valdez R (2010) Family history and personal genomics as tools for improving health in an era of evidence-based medicine. Am J Prev Med 39(2):184–188. doi:10.1016/j.amepre.2010.03.019PubMedCrossRefGoogle Scholar
  107. 107.
    Valdez R, Yoon PW, Qureshi N, Green RF, Khoury MJ (2010) Family history in public health practice: a genomic tool for disease prevention and health promotion. Annu Rev Public Health 31:69–87. doi:10.1146/annurev.publhealth.012809.103621Google Scholar
  108. 108.
    Jarvinen HJ, Mecklin JP, Sistonen P (1995) Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 108(5):1405–1411. doi:10.1016/0016-5085(95)90688-6PubMedCrossRefGoogle Scholar
  109. 109.
    Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P, McTiernan A, Offit K, Perlman J, Petersen G, Thomson E, Varricchio C (1997) Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium. JAMA 277(12):997–1003PubMedCrossRefGoogle Scholar
  110. 110.
    De Cosse JJ, Bulow S, Neale K, Jarvinen H, Alm T, Hultcrantz R, Moesgaard F, Costello C (1992) Rectal cancer risk in patients treated for familial adenomatous polyposis. The Leeds Castle Polyposis Group. Br J Surg 79(12):1372–1375PubMedCrossRefGoogle Scholar
  111. 111.
    Dunlop MG (2002) Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome. Gut 51(Suppl 5):V21–27Google Scholar
  112. 112.
    van Sprundel TC, Schmidt MK, Rookus MA, Brohet R, van Asperen CJ, Rutgers EJ, Van't Veer LJ, Tollenaar RA (2005) Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer 93(3):287–292. doi:10.1038/sj.bjc.6602703PubMedCentralPubMedCrossRefGoogle Scholar
  113. 113.
    Wacholder S, Hartge P, Prentice R, Garcia-Closas M, Feigelson HS, Diver WR, Thun MJ, Cox DG, Hankinson SE, Kraft P, Rosner B, Berg CD, Brinton LA, Lissowska J, Sherman ME, Chlebowski R, Kooperberg C, Jackson RD, Buckman DW, Hui P, Pfeiffer R, Jacobs KB, Thomas GD, Hoover RN, Gail MH, Chanock SJ, Hunter DJ (2010) Performance of common genetic variants in breast-cancer risk models. N Engl J Med 362(11):986–993. doi:10.1056/NEJMoa0907727PubMedCentralPubMedCrossRefGoogle Scholar
  114. 114.
    Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH (1995) High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 85(6):1504–1508PubMedGoogle Scholar
  115. 115.
    Andermann A, Blancquaert I, Beauchamp S, Costea I (2011) Guiding policy decisions for genetic screening: developing a systematic and transparent approach. Public Health Gen 14(1):9–16. doi:10.1159/000272898CrossRefGoogle Scholar
  116. 116.
    Nussbaum RL, McInnes RR, Willard HF (2007) Thompson & Thompson Genetics in Medicine. Elsevier Health Sciences, Makati CityGoogle Scholar
  117. 117.
    Health Council of the Netherlands (2008) Screening: between hope and hype. http://www.emgo.nl/files/Bonn%202010%20genetic%20screening%20criteria%20in%20the%20age%20of%20genomics.ppt. Accessed 20 Sep 2014

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Godfrey Grech
    • 1
    Email author
  • Christian Scerri
    • 2
  • Jeanesse Scerri
    • 3
  • Tomris Cesuroglu
    • 4
  1. 1.Department of Pathology, Faculty of Medicine and SurgeryUniversity of MaltaMsidaMalta
  2. 2.Department of Physiology and Biochemistry, Faculty of Medicine and SurgeryUniversity of MaltaMsidaMalta
  3. 3.Department of PathologyMater Dei HospitalMsidaMalta
  4. 4.Department of Social MedicineMaastricht UniversityMaastrichtNetherlands

Personalised recommendations