Skip to main content

Advertisement

Log in

Personalized genomic medicine

  • Lecture
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Personalized medicine provide to physicians a molecular makeup of each patient. Looking at the patient on this level helps the physician get a profile of the patient’s genetic distinction, or mapping. By investigating this genetic profile, medical professionals are then able to select patients, and use the found information to plan out a course of treatment that is much more in step with the way their body works. Personalize medicine is a direct extension of the genomic medicine that use genetic information to prevent or treat disease in adults or their children.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kidd JM, Cooper GM, Donahue WF et al (2008) Mapping and sequencing of structural variation from eight human genomes. Nature 453:56–64

    Article  CAS  PubMed  Google Scholar 

  2. Feero WG, Guttmacher AE, Collins FS (2010) Genomic medicine—an updated primer. N Engl J Med 362:2001–2011

    Article  CAS  PubMed  Google Scholar 

  3. Mallal S, Nolan D, Witt C et al (2002) Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 359:727–732

    Article  CAS  PubMed  Google Scholar 

  4. Hetherington S, Hughes AR, Mosteller M et al (2002) Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 359:1121–1122

    Article  CAS  PubMed  Google Scholar 

  5. Martin AM, Nolan D, Gaudieri S et al (2004) Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proc Natl Acad Sci USA 101:4180–4185

    Article  CAS  PubMed  Google Scholar 

  6. Hughes AR, Mosteller M, Bansal AT et al (2004) Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations. Pharmacogenomics 5:203–211

    Article  CAS  PubMed  Google Scholar 

  7. Phillips EJ, Wong GA, Kaul R et al (2005) Clinical and immunogenetic correlates of abacavir hypersensitivity. AIDS 19:979–981

    Article  CAS  PubMed  Google Scholar 

  8. Tesch N, Vogel M, Wasmuth JC, et al (2006) Abacavir-associated drug hypersensitivity is strongly associated with the human leukocyte antigen B-57 allele. In: Programs and abstracts of the 8th International congress on drug therapy in HIV infection, Glasgow, Scotland, November 12–16:44

  9. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jägel-Guedes E, Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A (2008) PREDICT-1 study team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 358(6):568–579

    Article  PubMed  Google Scholar 

  10. Clay PG (2002) The abacavir hypersensitivity reaction: a review. Clin Ther 24(10):1502–1514

    Article  CAS  PubMed  Google Scholar 

  11. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT (2004) Medical genetics: a marker for Stevens–Johnson syndrome. Nature 428:486

    Article  CAS  PubMed  Google Scholar 

  12. http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm

  13. Schwarz UI, Ritchie MD, Bradford Y, Li C, Dudek SM, Frye-Anderson A, Kim RB, Roden DM, Stein CM (2008) Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 358(10):999–1008

    Article  CAS  PubMed  Google Scholar 

  14. Borgiani P, Ciccacci C, Forte V, Romano S, Federici G, Novelli G (2007) Allelic variants in the CYP2C9 and VKORC1 loci and interindividual variability in the anticoagulant dose effect of warfarin in Italians. Pharmacogenomics 8(11):1545–1550

    Article  CAS  PubMed  Google Scholar 

  15. McDonald MG, Rieder MJ, Nakano M, Hsia CK, Rettie AE (2009) CYP4F2 is a vitamin K1 oxidase: an explanation for altered warfarin dose in carriers of the V433M variant. Mol Pharmacol 75(6):1337–1346

    Article  CAS  PubMed  Google Scholar 

  16. Borgiani P, Ciccacci C, Forte V, Sirianni E, Novelli L, Bramanti P, Novelli G (2009) CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population. Pharmacogenomics 10(2):261–266

    Article  CAS  PubMed  Google Scholar 

  17. US FDA: FDA approves updated warfarin (Coumadin) prescribing information www.fda.gov/bbs/topics/NEWS/2007/NEW01684.html. Accessed 15 Oct 2007

  18. Ageno W, Turpie AG, Steidl L et al (2001) Comparison of a daily fixed 2.5-mg warfarin dose with a 5-mg, international normalized ratio adjusted, warfarin dose initially following heart valve replacement. Am J Cardiol 88(1):40–44

    Google Scholar 

  19. Tan GM, Wu E, Lam YY, Yan BP (2010) Role of warfarin pharmacogenetic testing in clinical practice. Pharmacogenomics 11(3):439–448

    Article  CAS  PubMed  Google Scholar 

  20. Hirsh J, Guyatt G, Albers GW et al (2008) Executive summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 8th edn. Chest 133(Suppl 6):71

    Article  Google Scholar 

  21. Frueh FW, Amur S, Mummaneni P et al (2008) Pharmacogenomic biomarker information in drug labels approved by the United States Food and Drug Administration: prevalence of related drug use. Pharmacotherapy 28:992–998

    Article  PubMed  Google Scholar 

  22. Hamburg MA, Collins FS (2010) The Path to Personalized Medicine. N Engl J Med 363(4):301–304

    Article  CAS  PubMed  Google Scholar 

  23. Kang C, Riazuddin S, Mundorff J, Krasnewich D, Friedman P, Mullikin JC, Drayna D (2010) Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering. N Engl J Med 362(8):677–685

    Article  CAS  PubMed  Google Scholar 

  24. Büchel C, Watkins KE (2010) Genetic susceptibility to persistent stuttering. N Engl J Med 362(23):2226

    Article  PubMed  Google Scholar 

  25. Hindorff LA, Junkins HA, Manolio TA (2010) NHGRI Catalog of published genome-wide association studies. http://www.genome.gov/gwastudies. Accessed 7 June 2010

  26. Manolio TA (2010) Genomewide association studies and assessment of the risk of disease. N Engl J Med 363(2):166–176

    Article  CAS  PubMed  Google Scholar 

  27. Nevitt GJ, Hutchinson PE (1996) Psoriasis in the community: prevalence, severity and patients’ beliefs and attitudes towards the disease. Br J Dermatol 135:533–537

    Article  CAS  PubMed  Google Scholar 

  28. Sagoo GS, Cork MJ, Patel R, Tazi-Ahnini R (2004) Genome-wide studies of psoriasis susceptibility loci: a review. J Dermatol Sci 35(3):171–179

    Article  CAS  PubMed  Google Scholar 

  29. Christophers E (2001) Psoriasis—epidemiology and clinical spectrum. Clin Exp Dermatol 26:314–320

    Article  CAS  PubMed  Google Scholar 

  30. Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361(5):496–509

    Article  CAS  PubMed  Google Scholar 

  31. Farber EM, Nall ML (1974) The natural history of psoriasis in 5, 600 patients. Dermatologica 148:1–18

    Article  CAS  PubMed  Google Scholar 

  32. Trembath RC, Clough RL, Rosbotham JL et al (1997) Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum Mol Genet 6:813–820

    Article  CAS  PubMed  Google Scholar 

  33. de Cid R, Riveira-Munoz E, Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, Giardina E, Stuart PE, Nair R, Helms C, Escaramís G, Ballana E, Martín-Ezquerra G, den Heijer M, Kamsteeg M, Joosten I, Eichler EE, Lázaro C, Pujol RM, Armengol L, Abecasis G, Elder JT, Novelli G, Armour JA, Kwok PY, Bowcock A, Schalkwijk J, Estivill X (2009) Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 41(2):211–215

    Article  PubMed  Google Scholar 

  34. Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, Jacques PF, Rifai N, Selhub J, Robins SJ, Benjamin EJ, D’Agostino RB, Vasan RS (2006) Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 355(25):2631–2639

    Article  CAS  PubMed  Google Scholar 

  35. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847

    CAS  PubMed  Google Scholar 

  36. Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285:2486–2497

    Google Scholar 

  37. Khot UN, Khot MB, Bajzer CT et al (2003) Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 290:898–904

    Article  PubMed  Google Scholar 

  38. Greenland P, Knoll MD, Stamler J et al (2003) Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA 290:891–897

    Article  PubMed  Google Scholar 

  39. Magnus P, Beaglehole R (2001) The real contribution of the major risk factors to the coronary epidemics: time to end the “only-50%” myth. Arch Intern Med 161:2657–2660

    Article  CAS  PubMed  Google Scholar 

  40. Holm H, Gudbjartsson DF, Arnar DO, Thorleifsson G, Thorgeirsson G, Stefansdottir H, Gudjonsson SA, Jonasdottir A, Mathiesen EB, Njølstad I, Nyrnes A, Wilsgaard T, Hald EM, Hveem K, Stoltenberg C, Løchen ML, Kong A, Thorsteinsdottir U, Stefansson K (2010) Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet 42(2):117–122

    Article  CAS  PubMed  Google Scholar 

  41. MyocardialInfarctionGenetics Consortium, Kathiresan S, Voight BF, Purcell S, Musunuru K et al (2009) Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet 41(3):334–341

    Article  CAS  PubMed  Google Scholar 

  42. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, König IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H (2007) WTCCC and the Cardiogenics Consortium. Genomewide association analysis of coronary artery disease. N Engl J Med 357(5):443–453

    Article  CAS  PubMed  Google Scholar 

  43. Scheuner MT, Setodji CM, Pankow JS, Blumenthal RS, Keeler E (2010) General cardiovascular risk profile identifies advanced coronary artery calcium and is improved by family history: the multiethnic study of atherosclerosis. Circ Cardiovasc Genet 3(1):97–105

    Article  CAS  PubMed  Google Scholar 

  44. Anderwald C, Stadler M, Golay A, Krebs M, Petrie J, Luger A (2010) RISC Investigators Impact of family history on relations between insulin resistance, LDL cholesterol and carotid IMT in healthy adults. Heart 96(15):1191–1200

    Article  CAS  PubMed  Google Scholar 

  45. Congdon N, O’Colmain B, Klaver CC et al (2004) Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 122(4):477–485

    Article  PubMed  Google Scholar 

  46. Rivera A, Fisher SA, Fritsche LG et al (2005) Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum Mol Genet 14:3227–3236

    Article  CAS  PubMed  Google Scholar 

  47. Schmidt S, Hauser MA, Scott WK et al (2006) Cigarette smoking strongly modifies the association of LOC387715 and agerelated macular degeneration. Am J Hum Genet 78:852–864

    Article  CAS  PubMed  Google Scholar 

  48. Ricci F, Zampatti S, D’Abbruzzi F, Missiroli F, Martone C, Lepre T, Pietrangeli I, Sinibaldi C, Peconi C, Novelli G, Giardina E (2009) Typing of ARMS2 and CFH in age-related macular degeneration: case-control study and assessment of frequency in the Italian population. Arch Ophthalmol 127(10):1368–1372

    Article  CAS  PubMed  Google Scholar 

  49. DeAngelis MM, Ji F, Kim IK et al (2007) Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular degeneration. Arch Ophthalmol 125:49–54

    Article  CAS  PubMed  Google Scholar 

  50. Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358(24):2606–2617

    Article  CAS  PubMed  Google Scholar 

  51. Francis PJ, Hamon SC, Ott J, Weleber RG, Klein ML (2009) Polymorphisms in C2, CFB and C3 are associated with progression to advanced age related macular degeneration associated with visual loss. J Med Genet 46(5):300–307

    Article  CAS  PubMed  Google Scholar 

  52. Lee AY, Kulkarni M, Fang AM, Edelstein S, Osborn MP, Brantley MA (2010) The effect of genetic variants in SERPING1 on the risk of neovascular age-related macular degeneration. Br J Ophthalmol 94(7):915–917

    Article  CAS  PubMed  Google Scholar 

  53. Ennis S, Jomary C, Mullins R, Cree A, Chen X, Macleod A, Jones S, Collins A, Stone E, Lotery A (2008) Association between the SERPING1 gene and age-related macular degeneration: a two-stage case-control study. Lancet 372(9652):1828–1834

    Article  CAS  PubMed  Google Scholar 

  54. Gibson J, Cree A, Collins A, Lotery A, Ennis S (2010) Determination of a gene and environment risk model for age-related macular degeneration. Br J Ophthalmol [Epub ahead of print]

  55. Foulkes WD (2008) Inherited susceptibility to common cancers. N Engl J Med 359:2143

    Article  CAS  PubMed  Google Scholar 

  56. Public Health Agency of Canada (2010) http://www.phac-aspc.gc.ca/publicat/prccc-relccc/chap_2-eng.php

  57. Truong T et al (2010) International Lung Cancer Consortium: coordinated association study of 10 potential lung cancer susceptibility variants. Carcinogenesis 31(4):625–633

    Article  CAS  PubMed  Google Scholar 

  58. Raji OY, Agbaje OF, Duffy SW, Cassidy A, Field JK (2010) Incorporation of a genetic factor into an epidemiologic model for prediction of individual risk of lung cancer: the Liverpool Lung Project. Cancer Prev Res (Phila Pa) 3(5):664–669

    Google Scholar 

  59. American Cancer Society (2009) Cancer facts and figures (2009). http://www.cancer.gov/cancertopics/pdq/screening/breast/HealthProfessional/page3

  60. Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31:33–36

    Article  CAS  PubMed  Google Scholar 

  61. Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130

    Article  CAS  PubMed  Google Scholar 

  62. Ford D, Easton DF, Bishop DT et al (1994) Risks of cancer in BRCA1-mutation carriers Breast Cancer Linkage Consortium. Lancet 343:692–695

    Article  CAS  PubMed  Google Scholar 

  63. Marroni F, Aretini P, D’Andrea E et al (2004) Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations. Eur J Hum Genet 12:899–906

    Article  CAS  PubMed  Google Scholar 

  64. Raccomandazioni Di Buona Pratica Clinica—Linee guida Carcinoma Colorettale. Medici Medicina Generale, Settembre 2001

  65. National comprehensive cancer network (NCCN) (2010) NCCN clinical practice guidelines in oncology. Colorectal Cancer Screening V.1

  66. Burt RW, Jasperson KW (2008) APC-associated polyposis conditions. GENEReviews. http://www.ncbi.nlm.nih.gov/

  67. Baglioni S, Melean G, Gensini F, Santucci M, Scatizzi M, Papi L, Genuardi M (2005) A kindred with MYH-associated polyposis and pilomatricomas. Am J Med Genet 134A:212–214

    Article  PubMed  Google Scholar 

  68. Barnetson RA, Devlin L, Miller J, Farrington SM, Slater S, Drake AC, Campbell H, Dunlop MG, Porteous ME (2007) Germline mutation prevalence in the base excision repair gene, MYH, in patients with endometrial cancer. Clin Genet 72:551–555

    Article  CAS  PubMed  Google Scholar 

  69. Vasen HF, Mecklin JP, Khan PM, Lynch HT (1991) The international collaborative group on hereditary non-polyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum 34:424–425

    Article  CAS  PubMed  Google Scholar 

  70. 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 116:1453–1456

    Article  CAS  PubMed  Google Scholar 

  71. Kohlmann W, Gruber SB (2006) Hereditary non-polyposis colon cancer. GENEReviews. http://www.ncbi.nlm.nih.gov/

  72. Peltomaki P (2003) Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol 21:1174–1179

    Article  CAS  PubMed  Google Scholar 

  73. Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, Igari T, Koike M, Chiba M, Mori T (1997) Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet 17:271–272

    Article  CAS  PubMed  Google Scholar 

  74. Berends MJ, Wu Y, Sijmons RH, Mensink RG, van der Sluis T, Hordijk-Hos JM, de Vries EG, Hollema H, Karrenbeld A, Buys CH, van der Zee AG, Hofstra RM, Kleibeuker JH (2002) Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet 70:26–37

    Article  CAS  PubMed  Google Scholar 

  75. Aarnio M, Mecklin JP, Aaltonen LA, Nystrom-Lahti M, Jarvinen HJ (1995) Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer 64:430–433

    Article  CAS  PubMed  Google Scholar 

  76. Davis DA, Cohen PR (1995) Genitourinary tumors in men with Muir–Torre syndrome. J Amer Acad Dermatol 33:909–912

    Article  CAS  Google Scholar 

  77. Vasen HF, Wijnen JT, Menko FH, Kleibeuker JH, Taal BG, Griffioen G, Nagengast FM, Meijers-Heijboer EH, Bertario L, Varesco L, Bisgaard ML, Mohr J, Fodde R, Khan PM (1996) Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110:1020–1027

    Article  CAS  PubMed  Google Scholar 

  78. Rodriguez-Bigas MA, Vasen HF, Lynch HT, Watson P, Myrhoj T, Jarvinen HJ, Mecklin JP, Macrae F, St John DJ, Bertario L, Fidalgo P, Madlensky L, Rozen P (1998) Characteristics of small bowel carcinoma in hereditary nonpolyposis colorectal carcinoma international collaborative group on HNPCC. Cancer 83:240–244

    Article  CAS  PubMed  Google Scholar 

  79. Lin KM, Shashidharan M, Thorson AG, Ternent CA, Blatchford GJ, Christensen MA, Watson P, Lemon SJ, Franklin B, Karr B, Lynch J, Lynch HT (1998) Cumulative incidence of colorectal and extracolonic cancers in MLH1 and MSH2 mutation carriers of hereditary nonpolyposis colorectal cancer. J Gastrointest Surg 2:67–71

    Article  CAS  PubMed  Google Scholar 

  80. 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 81:214–218

    Article  CAS  PubMed  Google Scholar 

  81. Watson P, Butzow R, Lynch HT, Mecklin JP, Jarvinen HJ, Vasen HF, Madlensky L, Fidalgo P, Bernstein I (2001) The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 82:223–228

    Article  CAS  PubMed  Google Scholar 

  82. Lucci-Cordisco E, Zito I, Gensini F, Genuardi M (2003) Hereditary nonpolyposis colorectal cancer and related conditions. Am J Med Genet 122:325–334

    Article  Google Scholar 

  83. Bonis PA, Trikalinos TA, Chung M, Chew P, Ip S, DeVine D, Lau J (2007) Hereditary nonpolyposis colorectal cancer: diagnostic strategies and their implications. Evidence Report/Technology Assessment No. 150 (Prepared by Tufts-New England Medical Center Evidence-based Practice Center under Contract No. 290-02-0022). AHRQ Publication No. 07-E008. Rockville: agency for healthcare research and quality

  84. Harris R (1998) Genetic counselling and testing in Europe. J R Coll Physicians Lond 32(4):335–338

    CAS  PubMed  Google Scholar 

  85. Koch L, Svendsen MN (2005) Providing solutions—defining problems: the imperative of disease prevention in genetic counselling. Soc Sci Med 60(4):823–832

    Article  PubMed  Google Scholar 

  86. Meiser B, Dunn S (2000) Psychological impact of genetic testing for Huntington’s disease: an update of the literature. J Neurol Neurosurg Psychiatry 69(5):574–578

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Giuseppe Novelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Novelli, G. Personalized genomic medicine. Intern Emerg Med 5 (Suppl 1), 81–90 (2010). https://doi.org/10.1007/s11739-010-0455-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-010-0455-9

Keywords

Navigation