Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Essay
  • Published:

Screening for cancer with molecular markers: progress comes with potential problems

Nature Reviews Cancer volume 12, pages 368–371 (2012)Cite this article

Subjects

Abstract

Recent research has raised hopes for impressively accurate screening for cancer with molecular biomarkers. These molecular markers will probably be more sensitive and specific than older screening modalities, as well as easier to use. In this Essay, I argue that these sensitive screening tests might be clinically valuable — but that they will present unique issues in implementation and interpretation. These issues are likely to affect the way clinicians conduct screening and the way that they make diagnoses in individuals who screen positive for cancer.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Buys, S. S. et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 305, 2295–2303 (2011).

    Article  CAS  Google Scholar 

  2. Duffy, M. J. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin. Chem. 47, 624–630 (2001).

    CAS  PubMed  Google Scholar 

  3. Kulasingam, V., Pavlou, M. P. & Diamandis, E. P. Integrating high-throughput technologies in the quest for effective biomarkers for ovarian cancer. Nature Rev. Cancer 10, 371–378 (2010).

    Article  CAS  Google Scholar 

  4. Gigerenzer, G., Mata, J. & Frank, R. Public knowledge of benefits of breast and prostate cancer screening in Europe. J. Natl Cancer Inst. 101, 1216–1220 (2009).

    Article  Google Scholar 

  5. Schwartz, L. M., Woloshin, S., Fowler, F. J. Jr & Welch, H. G. Enthusiasm for cancer screening in the United States. JAMA 291, 71–78 (2004).

    Article  CAS  Google Scholar 

  6. Petricoin, E. F. et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359, 572–577 (2002).

    Article  CAS  Google Scholar 

  7. Visintin, I. et al. Diagnostic markers for early detection of ovarian cancer. Clin. Cancer Res. 14, 1065–1072 (2008).

    Article  CAS  Google Scholar 

  8. Ransohoff, D. F. Lessons from controversy: ovarian cancer screening and serum proteomics. J. Natl Cancer Inst. 97, 315–319 (2005).

    Article  CAS  Google Scholar 

  9. Zhu, C. S. et al. A framework for evaluating biomarkers for early detection: validation of biomarker panels for ovarian cancer. Cancer Prev. Res. 4, 375–383 (2011).

    Article  Google Scholar 

  10. Division of Cancer Prevention, US National Cancer Institute. The early detection research network, fifth report. NIH Publication 10–7696 (2011).

  11. Croswell, J. M., Baker, S. G., Marcus, P. M., Clapp, J. D. & Kramer, B. S. Cumulative incidence of false-positive test results in lung cancer screening: a randomized trial. Ann. Intern. Med. 152, 505–512 (2010).

    Article  Google Scholar 

  12. Villanueva, J. et al. Differential exoprotease activities confer tumor-specific serum peptidome patterns. J. Clin. Invest. 116, 271–284 (2006).

    Article  CAS  Google Scholar 

  13. Pang, W. W., Abdul-Rahman, P. S., Wan-Ibrahim, W. I. & Hashim, O. H. Can the acute-phase reactant proteins be used as cancer biomarkers? Int. J. Biol. Markers 25, 1–11 (2010).

    Article  CAS  Google Scholar 

  14. Grubb, R. L. et al. Serum prostate-specific antigen hemodilution among obese men undergoing screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol. Biomarkers Prev. 18, 748–751 (2009).

    Article  CAS  Google Scholar 

  15. Rundle, A., Richards, C. & Neugut, A. I. Hemodilution of prostate-specific antigen levels among obese men. Cancer Epidemiol. Biomarkers Prev. 18, 2343–2344 (2009).

    Article  Google Scholar 

  16. Loeb, S., Gashti, S. N. & Catalona, W. J. Exclusion of inflammation in the differential diagnosis of an elevated prostate-specific antigen (PSA). Urol. Oncol. 27, 64–66 (2009).

    Article  CAS  Google Scholar 

  17. Lu, H., Ouyang, W. & Huang, C. Inflammation, a key event in cancer development. Mol. Cancer Res. 4, 221–233 (2006).

    Article  Google Scholar 

  18. Hussain, S. P. & Harris, C. C. Inflammation and cancer: an ancient link with novel potentials. Int. J. Cancer 121, 2373–2380 (2007).

    Article  CAS  Google Scholar 

  19. Cole, P. & Morrison, A. S. Basic issues in population screening for cancer. J. Natl Cancer Inst. 64, 1263–1272 (1980).

    CAS  PubMed  Google Scholar 

  20. Dorigo, O. & Berek, J. S. Personalizing CA125 levels for ovarian cancer screening. Cancer Prev. Res. 4, 1356–1359 (2011).

    Article  CAS  Google Scholar 

  21. Black, W. C. Overdiagnosis: an underrecognized cause of confusion and harm in cancer screening. J. Natl Cancer Inst. 92, 1280–1282 (2000).

    Article  CAS  Google Scholar 

  22. Pollak, M. N. & Foulkes, W. D. Challenges to cancer control by screening. Nature Rev. Cancer 3, 297–303 (2003).

    Article  CAS  Google Scholar 

  23. Folkman, J. & Kalluri, R. Cancer without disease. Nature 427, 787 (2004).

    Article  CAS  Google Scholar 

  24. Thompson, I. M. et al. The influence of finasteride on the development of prostate cancer. N. Engl. J. Med. 349, 215–224 (2003).

    Article  CAS  Google Scholar 

  25. Esserman, L. Shieh, Y. & Thompson, I. Rethinking screening for breast cancer and prostate cancer. JAMA 302, 1685–1692 (2009).

    Article  CAS  Google Scholar 

  26. Kovacs, G. L. et al. Epidemiology of thyroid microcarcinoma found in autopsy series conducted in areas of different iodine intake. Thyroid 15, 152–157 (2005).

    Article  Google Scholar 

  27. Welch, H. G. & Black, W. C. Using autopsy series to estimate the disease “reservoir” for ductal carcinoma in situ of the breast: how much more breast cancer can we find? Ann. Intern. Med. 127, 1023–1028 (1997).

    Article  CAS  Google Scholar 

  28. Nielsen, M. Autopsy studies of the occurrence of cancerous, atypical and benign epithelial lesions in the female breast. APMIS Suppl. 10, 1–56 (1989).

    CAS  PubMed  Google Scholar 

  29. Biesheuvel, C., Barratt, A., Howard, K., Houssami, N. & Irwig, L. Effects of study methods and biases on estimates of invasive breast cancer overdetection with mammography screening: a systematic review. Lancet Oncol. 8, 1129–1138 (2007).

    Article  Google Scholar 

  30. Troyer, D. A. et al. Prostate cancer detected by methylated gene markers in histopathologically cancer-negative tissues from men with subsequent positive biopsies. Cancer Epidemiol. Biomarkers Prev. 18, 2717–2722 (2009).

    Article  CAS  Google Scholar 

  31. Jaffer, F. A. & Weissleder, R. Molecular imaging in the clinical arena. JAMA 293, 855–862 (2005).

    Article  CAS  Google Scholar 

  32. Kwon, R. S., Sahani, D. V. & Brugge, W. R. Gastrointestinal cancer imaging: deeper than the eye can see. Gastroenterology 128, 1538–1553 (2005).

    Article  Google Scholar 

  33. Wang, T. D. & Van Dam, J. Optical biopsy: a new frontier in endoscopic detection and diagnosis. Clin. Gastroenterol. Hepatol. 2, 744–753 (2004).

    Article  Google Scholar 

  34. Marten, K. et al. Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice. Gastroenterology 122, 406–414 (2002).

    Article  Google Scholar 

  35. Fletcher, R. H. Carcinoembryonic antigen. Ann. Intern. Med. 104, 66–73 (1986).

    Article  CAS  Google Scholar 

  36. Usadel, H. et al. Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. Cancer Res. 62, 371–375 (2002).

    CAS  PubMed  Google Scholar 

  37. Kawakami, K. et al. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J. Natl. Cancer Inst. 92, 1805–1811 (2000).

    Article  CAS  Google Scholar 

  38. Sorenson, G. D. Detection of mutated KRAS2 sequences as tumor markers in plasma/serum of patients with gastrointestinal cancer. Clin. Cancer Res. 6, 2129–2137 (2000).

    CAS  PubMed  Google Scholar 

  39. Nagasaka, T. et al. Analysis of fecal DNA methylation to detect gastrointestinal neoplasia. J. Natl. Cancer Inst. 101, 1244–1258 (2009).

    Article  CAS  Google Scholar 

  40. O'Shaughnessy, J. A. et al. Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin. Cancer Res. 8, 314–346 (2002).

    PubMed  Google Scholar 

  41. Cooper, K. et al. Chemoprevention of colorectal cancer: systematic review and economic evaluation. Health Technol. Assess. 14, 1–206 (2010).

    Article  CAS  Google Scholar 

  42. Cuzick, J. et al. Preventive therapy for breast cancer: a consensus statement. Lancet Oncol. 12, 496–503 (2011).

    Article  CAS  Google Scholar 

  43. Hruban, R. H., van der Riet, P., Erozan, Y. S. & Sidransky, D. Brief report: molecular biology and the early detection of carcinoma of the bladder-the case of Hubert H. Humphrey. N. Engl. J. Med. 330, 1276–1278 (1994).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Supported by U01 CA086400. Thanks are due to D. Brenner and S. Syngal for helpful comments.

Author information

Authors and Affiliations

  1. John A. Baron is at the Department of Medicine, University of North Carolina School of Medicine CB #7555, 4160-A Bioinformatics Building, Mason Farm Road, Chapel Hill, North Carolina 27599-7555, USA. jabaron@med.unc.edu,

    John A. Baron

Authors
  1. John A. Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baron, J. Screening for cancer with molecular markers: progress comes with potential problems. Nat Rev Cancer 12, 368–371 (2012). https://doi.org/10.1038/nrc3260

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc3260

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer