Digestive Diseases and Sciences

, Volume 60, Issue 3, pp 664–671 | Cite as

Blood-Based Tests for Colorectal Cancer Screening: Do They Threaten the Survival of the FIT Test?

  • Robert S. Bresalier
  • Scott Kopetz
  • Dean E. Brenner


Colorectal cancer is the second leading cause of cancer death in industrialized nations, accounting for 10 % of the total cancer burden with an individual lifetime risk of ~6 % in the USA (Siegel et al. in CA Cancer J Clin 62:9–29, 2014, American Cancer Society in Colorectal cancer facts and figures 2011–2013. American Cancer Society, Atlanta, 2011, Siegel et al. in CA Cancer J Clin 61:212–236, 2011). Although numerous screening methods have been incorporated into guidelines for colorectal cancer screening, no guideline includes a noninvasive blood-based test as a recommended option.


Colon cancer Screening Blood-based markers Fecal occult blood testing 


Conflict of interest



  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;62:9–29.CrossRefGoogle Scholar
  2. 2.
    American Cancer Society. Colorectal cancer facts and figures 2011–2013. Atlanta: American Cancer Society; 2011.Google Scholar
  3. 3.
    Siegel R, Ward E, Brawley O, Jemal A, Cancer statistics. The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61:212–236.CrossRefPubMedGoogle Scholar
  4. 4.
    Levin B, Lieberman DA, McFarland B, et al. American Cancer Society Colorectal Cancer Advisory Group, US Multi-Society Task Force, American College of Radiology Colon Cancer Committee. Gastroenterology. 2008;5:1570–1595.CrossRefGoogle Scholar
  5. 5.
    Centers for Disease C, Prevention. Vital signs: colorectal cancer screening test use—United States, 2012. MMWR. 2013;62:881–888.Google Scholar
  6. 6.
    Surveillance E, End Results Program. SEER Stat Fact Sheets: Colon and Rectum Cancer: Centers for Disease Control; 2014.
  7. 7.
    Green BB, Wang CY, Anderson ML, et al. An automated intervention with stepped increases in support to increase uptake of colorectal cancer screening: a randomized trial. Ann Intern Med. 2013;158:301–311. PMCID: 3953144.Google Scholar
  8. 8.
    National Center for Health Statistics. National Health Interview Survey (NHIS) public use data release: NHIS survey description. Hyattsville, MD: US Department of Health and Human Services, CDC, national Center for Health Statistics 2011; 2010. Scholar
  9. 9.
    Hoang TV, Gor BJ, Liang J, Esparza A, et al. Asian American Health Needs Assessment, 2006 community report. Houston, TX: The University of Texas MD Anderson Cancer Center; 2006.Google Scholar
  10. 10.
    Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of colonoscopy and death from colorectal cancer. Ann Intern Med. 2009;150:1–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Degnan N, Patnick J, Von Karsa L, eds. International Agency for Research on Cancer. European Guidelines for Quality Assurance in Colorectal cancer Screening and Diagnosis. 1st edn. Belgium: European Union; 2010.Google Scholar
  12. 12.
    Cancer Care Ontario. Colon cancer check 2010 program report. Cancer Care Ontario, Toronto Canada; 2012.
  13. 13.
    Imperiale T, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370:1287–1297.CrossRefPubMedGoogle Scholar
  14. 14.
    Hundt S, Haug U, Brenner H. Blood markers for early detection of colorectal cancer: a systematic review. Cancer Epidemiol Biomarkers Prev. 2007;16:1935–1953.CrossRefPubMedGoogle Scholar
  15. 15.
    Nielsen HJ, Jakobsen KV, Christensen IJ, Brunner N for the Danish Study Group on early Detection of Colorectal Cancer. Screening for colorectal cancer: possible improvements by risk assessment evaluation? Scan J Gastroenterol. 2011; 46:1283–1294.Google Scholar
  16. 16.
    Sanduleanu S, le Clercq CM, Dekker E, et al. Definition and taxonomy of interval colorectal cancers: a proposal for standardising nomenclature. Gut. 2014. doi: 10.1136/gutjnl-2014-307992.
  17. 17.
    Tao S, Hundt S, Haug U, Brenner H. Sensitivity estimates of blood-based tests for colorectal cancer detection: impact of overrepresentation of advanced stage disease. Am J Gastroenterol. 2011;106:242–253.CrossRefPubMedGoogle Scholar
  18. 18.
    Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Jr, Kinzler KW. Cancer genome landscapes. Science. 2013;339:1546–1558. PMCID: 3749880.Google Scholar
  19. 19.
    Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra24. PMCID: 4017867.Google Scholar
  20. 20.
    Diehl F, Li M, Dressman D, et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci. 2005;102:16368–16373.CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B. Detection and quantification of rare mutations with massive parallel sequencing. Proc Natl Acad Sci. 2011;108:9350–9535.CrossRefGoogle Scholar
  22. 22.
    Li M, Chen WD, Papadopoulos N, et al. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009;27:858–863.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Grutzmann R, Molnar B, Pilarsky C, et al. Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PLoS One. 2008;3:e3759.CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Lofton-Day C, Model F, Devos T, et al. DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem.. 2008;54:414–423.CrossRefPubMedGoogle Scholar
  25. 25.
    Church TR, Wandell M, Lofton-Day C, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut. 2014;63:317–325.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Hofsli E, Sjursen W, Prestvik WS, et al. Identification of serum microRNA profiles in colon cancer. Br J Cancer. 2013;108:1712–1719.CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Adamczyk B, Tharmalingam T, Rudd PM. Glycans as cancer biomarkers. Biochim Biophys Acta. 2012;1820:1347–1353.CrossRefPubMedGoogle Scholar
  28. 28.
    Patwa TH, Zhao J, Anderson MA, Simeone DM, Lubman DM. Screening of glycosylation patterns in serum using natural glycoprotein microarrays and multi-lectin fluorescence detection. Anal Chem. 2006;78:6411–6421.CrossRefPubMedGoogle Scholar
  29. 29.
    Yue T, Maupin KA, Fallon B, et al. Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers. PLoS One. 2011;6:e29180. PMCID: 3248411.Google Scholar
  30. 30.
    Zhao J, Patwa TH, Qiu W, et al. Glycoprotein microarrays with multi-lectin detection: unique lectin binding patterns as a tool for classifying normal, chronic pancreatitis and pancreatic cancer sera. Journal of proteome research.. 2007;6:1864–1874.CrossRefPubMedGoogle Scholar
  31. 31.
    Zhao J, Qiu W, Simeone DM, Lubman DM. N-linked glycosylation profiling of pancreatic cancer serum using capillary liquid phase separation coupled with mass spectrometric analysis. J Proteome Res. 2007;6:1126–1138.CrossRefPubMedGoogle Scholar
  32. 32.
    Qiu Y, Patwa TH, Xu L, et al. Plasma glycoprotein profiling for colorectal cancer biomarker identification by lectin glycoarray and lectin blot. J Proteome Res. 2008;7:1693–1703.CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Rho JH, Mead JR, Wright WS, et al. Discovery of sialyl Lewis A and Lewis X modified protein cancer biomarkers using high density antibody arrays. J Proteomics. 2014;96:291–299.CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Bresalier RS, Byrd JC, Tessler D, et al. A circulating ligand for galectin-3 is a haptoglobin-related glycoprotein elevated in individuals with colon cancer. Gastroenterology.. 2004;127:741–748.CrossRefPubMedGoogle Scholar
  35. 35.
    Giovannucci E, Pollak MN, Platz EA, et al. A prospective study of plasma Insulin-like growth factor and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomarkers Prev.. 2000;9:345–349.PubMedGoogle Scholar
  36. 36.
    Giovannucci E, Pollak M, Platz EA, et al. Insulin-like growth factor I (IGF-I), IGF-binding protein-3 and the risk of colorectal adenoma and cancer in the Nurses’ Health Study. Growth Horm IGF Res. 2000;10:S30–S301.CrossRefPubMedGoogle Scholar
  37. 37.
    Palmquist R, Stattin P, Rinaldi S, et al. Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Int J Cancer.. 2003;107:89–93.CrossRefGoogle Scholar
  38. 38.
    Cruz-Correa M, Cui H, Giardiello FM, et al. Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition. Gastroenterology. 2004;126:964–970.CrossRefPubMedGoogle Scholar
  39. 39.
    Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL, Feinberg AP. Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res. 2002;62:6442–6446.PubMedGoogle Scholar
  40. 40.
    Cui H, Cruz-Correa M, Giardiello FM, et al. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science. 2003;299:1753–1755.CrossRefPubMedGoogle Scholar
  41. 41.
    Woodson K, Flood A, Green L, et al. Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women. J Natl Cancer Inst. 2004;96:407–410.CrossRefPubMedGoogle Scholar
  42. 42.
    Narai S, Watanabe M, Hasegawa H, et al. Significance of Transforming growth factor beta 1 as a new tumor marker for colorectal cancer. Int J Cancer. 2002;97:508–511.CrossRefPubMedGoogle Scholar
  43. 43.
    Broll R, Erdmann H, Duchrow M, et al. Vascular endothelial growth factor (VEGF)—a valuable serum tumour marker in patients with colorectal cancer? Eur J Surg Oncol.. 2001;27:37–42.CrossRefPubMedGoogle Scholar
  44. 44.
    Takeda A, Shimada H, Imaseki H, et al. Clinical significance of serum vascular endothelial growth factor in colorectal cancer patients : correlation with clinicopathological factors and tumor markers. Oncol Rep. 2000;7:333–338.PubMedGoogle Scholar
  45. 45.
    Feldman AL, Alexander HR Jr, Bartlett DL, et al. A prospective analysis of plasma endostatin levels in colorectal cancer patients with liver metastases. Ann Surg Oncol. 2001;8:741–745.CrossRefPubMedGoogle Scholar
  46. 46.
    Peeters CF, Thomas CM, Sweep FC, Span PN, Wobbes T, Ruers TM. Elevated serum endothelin-1 levels in patients with colorectal cancer; relevance for prognosis. Int J Biol Markers. 2000;15:288–293.PubMedGoogle Scholar
  47. 47.
    Holten-Anderson MN, Christensen IJ, Nielsen HJ, et al. Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer. Clin Cancer Res. 2002;8:156–164.Google Scholar
  48. 48.
    Alexiou D, Karayiannakis AJ, Syrigos KN, et al. Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery. Eur J Cancer. 2001;37:2392–2397.CrossRefPubMedGoogle Scholar
  49. 49.
    Ladd JJ, Busald T, Johnson MM, et al. Increased plasma levels of the APC-interacting protein MAPRE-1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women. Cancer Prv Res. 2012;5:655–664.CrossRefGoogle Scholar
  50. 50.
    Scanlan MJ, Welt S, Gordon CM, et al. Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets. Cancer Res. 2002;62:4041–4047.PubMedGoogle Scholar
  51. 51.
    Lu H, Goodell V, Disis ML. Targeting serum antibody for cancer diagnosis: a focus on colorectal cancer. Expert Opin Ther Targets. 2007;11:235–244.CrossRefPubMedGoogle Scholar
  52. 52.
    Nam MJ, Madoz-Gurpide J, Wang H, et al. Molecular profiling of the immune response in colon cancer using protein microarrays: occurrence of autoantibodies to ubiquitin C-terminal hydrolase L3. Proteomics.. 2003;3:2108–2115.CrossRefPubMedGoogle Scholar
  53. 53.
    Zaenker P, Ziman MR. Serologic autoantibodies as diagnostic cancer biomarkers—a review. Cancer Epidemiol Biomarkers Prev. 2013;22:2161–2181.CrossRefPubMedGoogle Scholar
  54. 54.
    Reipert BM, Tanneberger S, Pannetta A, et al. Increase in autoantibodies against Fas (CD95) during carcinogenesis in the human colon: a hope for the immunoprevention of cancer? Cancer Immunol Immunother. 2005;54:1038–1042.CrossRefPubMedGoogle Scholar
  55. 55.
    He Y, Wu Y, Mou Z, et al. Proteomics-based identification of HSP60 as a tumor-associated antigen in colorectal cancer. Proteomics Clin Appl. 2007;1:336–342.CrossRefPubMedGoogle Scholar
  56. 56.
    Chen Y, Lin P, Qiu S, et al. Autoantibodies to Ca2+ binding protein Calnuc is a potential marker in colon cancer detection. Int J Oncol. 2007;30:1137–1144.PubMedGoogle Scholar
  57. 57.
    Liu W, Wang P, Li Z, et al. Evaluation of tumour-associated antigen (TAA) miniarray in immunodiagnosis of colon cancer. Scand J Immunol. 2009;69:57–63.CrossRefPubMedGoogle Scholar
  58. 58.
    Lim SH, Becker TM, Chua W, Ng WL, de Souza P, Spring KJ. Circulating tumour cells and the epithelial mesenchymal transition in colorectal cancer. J Clin Pathol. 2014;67:848–853.CrossRefPubMedGoogle Scholar
  59. 59.
    Zhang Z, Nagrath S. Microfluidics and cancer: are we there yet? Biomed Microdevices. 2013;15:595–609. PMCID: 4017600.Google Scholar
  60. 60.
    Murlidhar V, Zeinali M, Grabauskiene S, et al. A radial flow microfluidic device for ultra-high-throughput affinity-based isolation of circulating tumor cells. Small. 2014;10:4895–4904.CrossRefPubMedGoogle Scholar
  61. 61.
    Pepe MS, Feng Z, Janes H, Bossuyt PM, Potter JD. Pivotal evaluation of the accuracy of a biomarker used for classification and prediction: Standards for study design. J Natl cancer Instit. 2008;100:1432–1438.CrossRefGoogle Scholar
  62. 62.
    Surinova S, Sciess R, Huttenhein R, Ceciello F, Wollscheid B, Aebersold R. On the development of plasma protein biomarkers. J Proteome Res. 2011;10:5–16.CrossRefPubMedGoogle Scholar
  63. 63.
    Toth K, Sipos F, Kalmar A, et al. Detection of methylated Sept9 in plasma is a reliable screening method for both left- and right-sided colon cancers. PLOS One. 2012;7:e46000.CrossRefPubMedCentralPubMedGoogle Scholar
  64. 64.
    Ladabaum U, Allen J, Wandell M, Ramsey S. Colorectal cancer screening with blood-based biomarkers: cost-effectiveness of methylated Septin 9 DNA versus current strategies. Cancer Epidemiol Biomarkers Prev. 2013;22:1567–1576.CrossRefPubMedGoogle Scholar
  65. 65.
    Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other vesicles. Annu Rev Cell Biol. 2014;30:255–289.CrossRefGoogle Scholar
  66. 66.
    Tuck MK, Chan DW, Chia D, et al. Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res. 2009;8:113–117.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Robert S. Bresalier
    • 1
  • Scott Kopetz
    • 2
  • Dean E. Brenner
    • 3
  1. 1.Department of Gastroenterology, Hepatology and NutritionThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of GI Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Medical OncologyThe University of MichiganAnn ArborUSA

Personalised recommendations