Startseite Medizin The side effects of translational omics: overtesting, overdiagnosis, overtreatment
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

The side effects of translational omics: overtesting, overdiagnosis, overtreatment

  • Eleftherios P. Diamandis EMAIL logo und Michelle Li
Veröffentlicht/Copyright: 7. Oktober 2015
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 54 Heft 3

Abstract

High-throughput technologies such as next-generation genomics, transcriptomics and proteomics are capable of generating massive amounts of data quickly, and at relatively low costs. It is tempting to use this data for various medical applications including preclinical disease detection and for prediction of disease predisposition. Pilot projects, initiated by various research groups and Google, are currently underway, but results with not be available for a few years. We here summarize some possible difficulties with these approaches, by using examples from already tried cancer and other screening programs. Population screening, especially with multiparametric algorithms, will identify at least some false positive parameters and screening programs will identify abnormal results in otherwise healthy individuals. Whole genome sequencing will identify genetic changes of unknown significance and may not predict accurately future disease predisposition if the disease is also influenced by environmental factors. In screening programs, if the disease is rare, the positive predictive value of the test will be low, even if the test has excellent sensitivity and specificity. False positive results may require invasive procedures to delineate. Furthermore, screening programs are not effective if the cancer grows quickly, and will identify indolent forms of the disease with slow-growing tumors. It has also been recently shown that for some cancers, more intensive and radical treatments do not usually lead to better clinical outcomes. We conclude that new omics testing technologies should avoid overdiagnosis and overtreatment and need to be evaluated for overall clinical benefit before introduction to the clinic.

Keywords: escape from cure; high-throughput omics; incidental findings; indolent disease; overdiagnosis; overtesting; overtreatment; side effects
Corresponding author: Eleftherios P. Diamandis, MD, PhD, FRCP(C), FRSC, Head of Clinical Biochemistry, Mount Sinai Hospital and University Health Network, 60 Murray St. Box 32, Floor 6, Rm L6-201, Toronto, M5T 3L9 ON, Canada, Phone: +(416) 586-8443, E-mail: ; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

References

1. Hood L, Balling R, Auffray C. Revolutionizing medicine in the 21st century through systems approaches. Biotechnol J 2012;7:992–1001.10.1002/biot.201100306Suche in Google Scholar PubMed PubMed Central

2. Flores M, Glusman G, Brogaard K, Price ND, Hood L. P4 medicine: how systems medicine will transform the healthcare sector and society. Per Med 2013;10:565–76.10.2217/pme.13.57Suche in Google Scholar PubMed PubMed Central

3. Xu S, Zhang Y, Jia L, Mathewson KE, Jang K-I, Kim J, et al. Soft microfluidic assemblies of sensors, circuits, and radios for the skin. Science 2014;344:70–4.10.1126/science.1250169Suche in Google Scholar PubMed

4. Gibbs WW. Medicine gets up close and personal. Nature 2014;506:144–5.10.1038/506144aSuche in Google Scholar PubMed

5. Hood L, Lovejoy JC, Price ND. Integrating big data and actionable health coaching to optimize wellness. BMC Med 2015;13:4.10.1186/s12916-014-0238-7Suche in Google Scholar PubMed PubMed Central

6. Kaiser J. Google X sets out to define healthy human. Science insider 2014. Available from: http://scim.ag/googlehuman.Suche in Google Scholar

7. Diamandis EP. The hundred person wellness project and Google’s baseline study: medical revolution or unnecessary and potentially harmful over-testing? BMC Med 2015;13:5.10.1186/s12916-014-0239-6Suche in Google Scholar PubMed PubMed Central

8. Wilcken B. Newborn screening: gaps in the evidence. Science 2013;342:197–8.10.1126/science.1243944Suche in Google Scholar PubMed

9. Wilson MG, Jungner G. Principles and practice for screening for disease. Public Health Papers 34; Geneva: World Health Organization, 1968.Suche in Google Scholar

10. Welch HG. Overdiagnosis and mammography screening. Br Med J 2009;339:182–3.10.1136/bmj.b1425Suche in Google Scholar PubMed

11. Skeggs LT Jr. Persistence…and prayer. From the artificial kidney to the autoanalyzer. Clin Chem 2000;46:1425–36.10.1093/clinchem/46.9.1425Suche in Google Scholar

12. Anonymous. Bargain genome. Nature 2014;505:458–9.Suche in Google Scholar

13. Chrystoja CC, Diamandis EP. Whole genome sequencing as a diagnostic test: challenges and opportunities. Clin Chem 2014;60:1–10.Suche in Google Scholar

14. Yang Y, Muzay DM, Reid JG, Bainbridge MN, Willis A, Ward PA, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013;369:1502–11.10.1056/NEJMoa1306555Suche in Google Scholar PubMed PubMed Central

15. Esplin ED, Oei L, Snyder MP. Personalized sequencing and the future of medicine: discovery, diagnosis and defeat of disease. Pharmacogenomics 2014;15:1771–90.10.2217/pgs.14.117Suche in Google Scholar PubMed PubMed Central

16. Van Allen EM, Wagle N, Stojanov P, Perrin DL, Cibulskis K, Marlow S, et al. Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine. Nat Med 2014;20:682–8.10.1038/nm.3559Suche in Google Scholar PubMed PubMed Central

17. Garralda E, Paz K, López-Casas PP, Jones S, Katz A, Kann LM, et al. Integrated next-generation sequencing and avatar mouse models for personalized cancer treatment. Clin Cancer Res 2014;20:2476–84.10.1158/1078-0432.CCR-13-3047Suche in Google Scholar PubMed PubMed Central

18. Ellis MJ. Mutational analysis of breast cancer: guiding personalized treatments. Breast 2013;22:S19–21.10.1016/j.breast.2013.07.003Suche in Google Scholar PubMed PubMed Central

19. Anonymous. The FDA and me. Nature 2013;504:7–8.10.1038/504007bSuche in Google Scholar PubMed

20. Annas GD, Sherman E. 23andMe and the FDA. N Engl J Med 2014;370:985–8.10.1056/NEJMp1316367Suche in Google Scholar PubMed

21. Church G. Genomics is mired in misunderstanding. Nature 2013;502:143.10.1038/502143aSuche in Google Scholar PubMed

22. Roberts NJ, Vogelstein JT, Parmigiani G, Kinzler KW, Vogelstein B, Valculescu VE. The predictive capacity of personal genome sequencing. Sci Transl Med 2012;4:133ra58.10.1126/scitranslmed.3003380Suche in Google Scholar PubMed PubMed Central

23. Castle PE. Teaching moment: why promising biomarkers do not always translate into clinically useful tests. J Clin Oncol 2014;32:359–61.10.1200/JCO.2013.52.3076Suche in Google Scholar PubMed

24. Esserman LJ, Thompson IM Jr, Reid B. Overdiagnosis and overtreatment of cancer. An opportunity for improvement. J Am Med Assoc 2013;310:397–8.10.1001/jama.2013.108415Suche in Google Scholar PubMed

25. Schiffman M, Solomon D. Cervical – cancer screening with human papillomavirus and cytologic cotesting. N Engl J Med 2013;369:2324–31.10.1056/NEJMcp1210379Suche in Google Scholar

26. Levin TR, Corley DA. Colorectal – cancer screening – coming of age. N Engl J Med 2013;396:1164–6.Suche in Google Scholar

27. Kistler CE. Colorectal – cancer incidence and mortality after screening. N Engl J Med 2013;396:2354–5.Suche in Google Scholar

28. Bleyer A, Welch HG. Effect of three decades of screening mammography on breast – cancer incidence. N Engl J Med 2012;367:1998–2005.10.1056/NEJMoa1206809Suche in Google Scholar

29. Biller-Andorno N, Juni P. Abolishing mammography screening programs. A view from the Swiss Medical Board. N Eng J Med 2014;370:1965–7.10.1056/NEJMp1401875Suche in Google Scholar

30. Aberle DR, DeMello S, Berg CD, Black WC, Brewer B, Church TR, et al. Results of the two incidence screenings in the national lunch screening trial. N Engl J Med 2013;369:920–31.10.1056/NEJMoa1208962Suche in Google Scholar

31. Maldonado F, Peikert T, Midthun D. Cancer in pulmonary nodules detected on first screening CT. N Engl J Med 2013;396:2060–1.Suche in Google Scholar

32. McWilliams A, Tammemagi MC, Mayo JR, Roberts H, Liu G, Soghrati K, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med 2013:369:910–9.10.1056/NEJMoa1214726Suche in Google Scholar

33. Moyer VA. Screening for lung cancer: U.S. preventive services task force recommendation statement. Ann Intern Med 2014;160:330–8.Suche in Google Scholar

34. Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK collaborative trial of ovarian cancer screening (UKCTOCS). Lancet Oncol 2009;10:327–40.10.1016/S1470-2045(09)70026-9Suche in Google Scholar

35. Andriole GL, Crawford ED, Grubb RL III, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009:360:1310–9. Erratum in: N Engl J Med 2009;360:1797.Suche in Google Scholar

36. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320–8.10.1056/NEJMoa0810084Suche in Google Scholar PubMed

37. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med 2012;366:981–90. Erratum in: N Engl J Med 2012;366:2137.Suche in Google Scholar

38. Wade J, Rosario DJ, Macefield RC, Avery KN, Salter CE, Goodwin ML, et al. Physchological impact of prostate biopsy: physical symptoms, anxiety, and depression. J Clin Oncol 2013;31:4235–41.10.1200/JCO.2012.45.4801Suche in Google Scholar PubMed

39. Basch E, Oliver TK, Vickers A, Thompson I, Kantoff P, Parnes H, et al. Screening for prostate cancer with prostate-specific antigen testing: American society of clinical oncology provisional clinical opinion. J Clin Oncol 2012;30:3020–5.10.1200/JCO.2012.43.3441Suche in Google Scholar PubMed PubMed Central

40. Thompson IM, Tangen CM. Prostate cancer – uncertainty and a way forward. N Engl J Med 2012;376:270–1.Suche in Google Scholar

41. Hayes JH, Barry MJ. Screening for prostate cancer with the prostate-specific antigen test: a review of current evidence. J Am Med Assoc 2014;311:1143–9.10.1001/jama.2014.2085Suche in Google Scholar PubMed

42. Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012;367:203–13.10.1056/NEJMoa1113162Suche in Google Scholar

43. Froehner M, Writh MP. Early prostate cancer – treat or watch? N Engl J Med 2011;365:568–9.10.1056/NEJMc1106325Suche in Google Scholar

44. Solomon BD. Incidentalomas in genomics and radiology. N Engl J Med 2014;370:988–90.10.1056/NEJMp1310471Suche in Google Scholar

45. MacArthur DG, Manolio TA, Dimmock DP, Rehm HL, Shendure J, Abecasis GR, et al. Guidelines for investigating causality of sequence variants in human disease. Nature 2014;508:469–76.10.1038/nature13127Suche in Google Scholar

46. Fisher B, Redmond C, Poisson R, Margolese R, Wolmark N, Wickerham L, et al. Eight-year results of randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989;320:822–8.10.1056/NEJM198903303201302Suche in Google Scholar

47. Anonymous. Prostate cancer: send away the PSA? Lancet 2012;380:307.10.1016/S0140-6736(12)61232-XSuche in Google Scholar

Received: 2015-8-6
Accepted: 2015-8-28
Published Online: 2015-10-7
Published in Print: 2016-3-1

©2016 by De Gruyter

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. The way of prostate cancer diagnostics
  4. Review
  5. Statistical methods used in the calculation of geriatric reference intervals: a systematic review
  6. Opinion Paper
  7. The side effects of translational omics: overtesting, overdiagnosis, overtreatment
  8. Genetics and Molecular Diagnostics
  9. Rapid detection of non-deletional mutations causing α-thalassemia by multicolor melting curve analysis
  10. General Clinical Chemistry and Laboratory Medicine
  11. Patient pools and the use of “patient means” are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay
  12. Long-term stability of glucose: 96-h study using Terumo Glycaemia tubes
  13. Glucose is stable during prolonged storage in un-centrifuged Greiner tubes with liquid citrate buffer, but not in serum and NaF/KOx tubes
  14. Croatian laboratories have a good knowledge of the proper detection and management of hemolyzed, icteric and lipemic samples
  15. Fetal exposure to ethanol: relationship between ethyl glucuronide in maternal hair during pregnancy and ethyl glucuronide in neonatal meconium
  16. Comparing the effect of isotopically labeled or structural analog internal standards on the performance of a LC-MS/MS method to determine ciclosporin A, everolimus, sirolimus and tacrolimus in whole blood
  17. Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study
  18. Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients – a retrospective study
  19. Reference Values and Biological Variations
  20. Assessment of serum free light chain levels in healthy adults immediately after marathon running
  21. Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients
  22. Cancer Diagnostics
  23. An epidemiology-based model as a tool to monitor the outbreak of inappropriateness in tumor marker requests: a national scale study
  24. Comparative analysis of prostate cancer specific biomarkers PCA3 and ERG in whole urine, urinary sediments and exosomes
  25. Infectious Diseases
  26. Comparative evaluation of the Aptima HIV-1 Quant Dx assay and COBAS TaqMan HIV-1 v2.0 assay using the Roche High Pure System for the quantification of HIV-1 RNA in plasma
  27. Evaluating the use of procalcitonin in an asymptomatic, HIV-infected antiretroviral therapy-naïve, South African cohort
  28. Diabetes
  29. Early prediction of gestational diabetes: a practical model combining clinical and biochemical markers
  30. Letters to the Editors
  31. Highly-trained dogs’ olfactory system for detecting biochemical recurrence following radical prostatectomy
  32. More on the accuracy of the Architect enzymatic assay for hemoglobin A1c and its traceability to the IFCC reference system
  33. Assessing quality from an accuracy-based HbA1c proficiency survey
  34. HbG-Honolulu interferes with some cation-exchange HPLC HbA1c assays
  35. Between analyser differences in chloride measurements and thus anion gap cause different interpretations of the acid-base balance
  36. Non-albumininuric proteinuria: a urinary tubular marker in the diagnosis of diabetic kidney disease
  37. International Normalized Ratio (INR) testing: analytical and clinical performance of four point-of-care devices versus central laboratory instrumentation analysis
  38. Genetic screening of the makorin ring finger 3 gene in girls with idiopathic central precocious puberty
  39. Practical approach for medical validation of therapeutic drug monitoring results
  40. Marked elevation of procalcitonin in a patient with a drug related infusion reaction to rituximab
https://doi.org/10.1515/cclm-2015-0762
Schlagwörter für diesen Artikel
escape from cure; high-throughput omics; incidental findings; indolent disease; overdiagnosis; overtesting; overtreatment; side effects

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. The way of prostate cancer diagnostics
  4. Review
  5. Statistical methods used in the calculation of geriatric reference intervals: a systematic review
  6. Opinion Paper
  7. The side effects of translational omics: overtesting, overdiagnosis, overtreatment
  8. Genetics and Molecular Diagnostics
  9. Rapid detection of non-deletional mutations causing α-thalassemia by multicolor melting curve analysis
  10. General Clinical Chemistry and Laboratory Medicine
  11. Patient pools and the use of “patient means” are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay
  12. Long-term stability of glucose: 96-h study using Terumo Glycaemia tubes
  13. Glucose is stable during prolonged storage in un-centrifuged Greiner tubes with liquid citrate buffer, but not in serum and NaF/KOx tubes
  14. Croatian laboratories have a good knowledge of the proper detection and management of hemolyzed, icteric and lipemic samples
  15. Fetal exposure to ethanol: relationship between ethyl glucuronide in maternal hair during pregnancy and ethyl glucuronide in neonatal meconium
  16. Comparing the effect of isotopically labeled or structural analog internal standards on the performance of a LC-MS/MS method to determine ciclosporin A, everolimus, sirolimus and tacrolimus in whole blood
  17. Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study
  18. Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients – a retrospective study
  19. Reference Values and Biological Variations
  20. Assessment of serum free light chain levels in healthy adults immediately after marathon running
  21. Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients
  22. Cancer Diagnostics
  23. An epidemiology-based model as a tool to monitor the outbreak of inappropriateness in tumor marker requests: a national scale study
  24. Comparative analysis of prostate cancer specific biomarkers PCA3 and ERG in whole urine, urinary sediments and exosomes
  25. Infectious Diseases
  26. Comparative evaluation of the Aptima HIV-1 Quant Dx assay and COBAS TaqMan HIV-1 v2.0 assay using the Roche High Pure System for the quantification of HIV-1 RNA in plasma
  27. Evaluating the use of procalcitonin in an asymptomatic, HIV-infected antiretroviral therapy-naïve, South African cohort
  28. Diabetes
  29. Early prediction of gestational diabetes: a practical model combining clinical and biochemical markers
  30. Letters to the Editors
  31. Highly-trained dogs’ olfactory system for detecting biochemical recurrence following radical prostatectomy
  32. More on the accuracy of the Architect enzymatic assay for hemoglobin A1c and its traceability to the IFCC reference system
  33. Assessing quality from an accuracy-based HbA1c proficiency survey
  34. HbG-Honolulu interferes with some cation-exchange HPLC HbA1c assays
  35. Between analyser differences in chloride measurements and thus anion gap cause different interpretations of the acid-base balance
  36. Non-albumininuric proteinuria: a urinary tubular marker in the diagnosis of diabetic kidney disease
  37. International Normalized Ratio (INR) testing: analytical and clinical performance of four point-of-care devices versus central laboratory instrumentation analysis
  38. Genetic screening of the makorin ring finger 3 gene in girls with idiopathic central precocious puberty
  39. Practical approach for medical validation of therapeutic drug monitoring results
  40. Marked elevation of procalcitonin in a patient with a drug related infusion reaction to rituximab
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2026 De Gruyter Brill
Heruntergeladen am 23.1.2026 von https://www.degruyterbrill.com/document/doi/10.1515/cclm-2015-0762/html?lang=de
Button zum nach oben scrollen