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Licensed Unlicensed Requires Authentication Published by De Gruyter October 7, 2015

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

  • Eleftherios P. Diamandis EMAIL logo and Michelle Li


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.

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


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.201100306Search 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.13.57Search 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.1250169Search in Google Scholar PubMed

4. Gibbs WW. Medicine gets up close and personal. Nature 2014;506:144–5.10.1038/506144aSearch 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/s12916-014-0238-7Search in Google Scholar PubMed PubMed Central

6. Kaiser J. Google X sets out to define healthy human. Science insider 2014. Available from: 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/s12916-014-0239-6Search in Google Scholar PubMed PubMed Central

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

10. Welch HG. Overdiagnosis and mammography screening. Br Med J 2009;339:182–3.10.1136/bmj.b1425Search 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/46.9.1425Search in Google Scholar

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

13. Chrystoja CC, Diamandis EP. Whole genome sequencing as a diagnostic test: challenges and opportunities. Clin Chem 2014;60:1–10.Search 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/NEJMoa1306555Search 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.14.117Search 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.3559Search 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-13-3047Search 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.2013.07.003Search in Google Scholar PubMed PubMed Central

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

20. Annas GD, Sherman E. 23andMe and the FDA. N Engl J Med 2014;370:985–8.10.1056/NEJMp1316367Search in Google Scholar PubMed

21. Church G. Genomics is mired in misunderstanding. Nature 2013;502:143.10.1038/502143aSearch 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.3003380Search 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.2013.52.3076Search 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.2013.108415Search 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/NEJMcp1210379Search in Google Scholar

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

27. Kistler CE. Colorectal – cancer incidence and mortality after screening. N Engl J Med 2013;396:2354–5.Search 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/NEJMoa1206809Search 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/NEJMp1401875Search 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/NEJMoa1208962Search 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.Search 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/NEJMoa1214726Search 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.Search 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)70026-9Search 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.Search 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/NEJMoa0810084Search 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.Search 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.2012.45.4801Search 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.2012.43.3441Search 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.Search 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.2014.2085Search 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/NEJMoa1113162Search in Google Scholar

43. Froehner M, Writh MP. Early prostate cancer – treat or watch? N Engl J Med 2011;365:568–9.10.1056/NEJMc1106325Search in Google Scholar

44. Solomon BD. Incidentalomas in genomics and radiology. N Engl J Med 2014;370:988–90.10.1056/NEJMp1310471Search 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/nature13127Search 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/NEJM198903303201302Search in Google Scholar

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

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