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The colorectal cancer epidemic: challenges and opportunities for primary, secondary and tertiary prevention

British Journal of Cancervolume 119pages785792 (2018) | Download Citation



Colorectal cancer (CRC) is both one of the most common and one of the most preventable cancers globally, with powerful but strongly missed potential for primary, secondary and tertiary prevention. CRC incidence has traditionally been the highest in affluent Western countries, but it is now increasing rapidly with economic development in many other parts of the world. CRC shares several main risk factors, such as smoking, excessive alcohol consumption, physical inactivity and being overweight, with other common diseases; therefore, primary prevention efforts to reduce these risk factors are expected to have multiple beneficial effects that extend beyond CRC prevention, and should have high public health impact. A sizeable reduction in the incidence and mortality of CRC can also be achieved by offering effective screening tests, such as faecal immunochemical tests, flexible sigmoidoscopy and colonoscopy, in organised screening programmes which have been implemented in an increasing number of countries. Countries with early and high uptake rates of effective screening have exhibited major declines in CRC incidence and mortality, in contrast to most other countries. Finally, increasing evidence shows that the prognosis and quality of life of CRC patients can be substantially improved by tertiary prevention measures, such as the administration of low-dose aspirin and the promotion of physical activity.

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  1. 1.

    Ferlay, J. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, E359–386 (2015).

  2. 2.

    Babaei, M. et al. Minimally invasive colorectal cancer surgery in Europe: implementation and outcomes. Med. (Baltim.) 95, e3812 (2016).

  3. 3.

    Brenner, H., Kloor, M. & Pox, C. P. Colorectal cancer. Lancet 383, 1490–1502 (2014).

  4. 4.

    Babaei, M. et al. Neoadjuvant therapy in rectal cancer patients with clinical Stage II to III across European countries: variations and outcomes. Clin. Colorectal Cancer 17, e129–e142 (2018).

  5. 5.

    Babaei, M. et al. Administration of adjuvant chemotherapy for stage II-III colon cancer patients: an European population-based study. Int. J. Cancer 142, 1480–1489 (2018).

  6. 6.

    Jemal, A. et al. Annual report to the nation on the status of cancer, 1975–2014, featuring survival. J. Natl. Cancer Inst. 109 (2017).

  7. 7.

    Holleczek, B. et al. On-going improvement and persistent differences in the survival for patients with colon and rectum cancer across Europe 1999–2007—Results from the EUROCARE-5 study. Eur. J. Cancer 51, 2158–2168 (2015).

  8. 8.

    Siegel, R. L. et al. Colorectal cancer statistics, 2017. CA Cancer J. Clin. 67, 177–193 (2017).

  9. 9.

    Arnold, M. et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut 66, 683–691 (2017).

  10. 10.

    Brenner, H., Schrotz-King, P., Holleczek, B., Katalinic, A. & Hoffmeister, M. Declining bowel cancer incidence and mortality in Germany: an analysis of time trends in the first ten years after the introduction of screening colonoscopy. Dtsch. Ärzteblatt Int. 113, 101–106 (2016).

  11. 11.

    Chen, C., Lacke, E., Stock, C., Hoffmeister, M. & Brenner, H. Colonoscopy and sigmoidoscopy use among older adults in different countries: a systematic review. Prev. Med. 103, 33–42 (2017).

  12. 12.

    Siegel, R. L. et al. Colorectal cancer incidence patterns in the United States, 1974–2013. J. Natl. Cancer Inst. 109 (2017).

  13. 13.

    Botteri, E. et al. Smoking and colorectal cancer: a meta-analysis. JAMA 300, 2765–2778 (2008).

  14. 14.

    Bagnardi, V. et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br. J. Cancer 112, 580–593 (2015).

  15. 15.

    Freisling, H. et al. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe. Br. J. Cancer 116, 1486–1497 (2017).

  16. 16.

    Vieira, A. R. et al. Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR continuous update project. Ann. Oncol. 28, 1788–1802 (2017).

  17. 17.

    Boyle, T., Keegel, T., Bull, F., Heyworth, J. & Fritschi, L. Physical activity and risks of proximal and distal colon cancers: a systematic review and meta-analysis. J. Natl. Cancer Inst. 104, 1548–1561 (2012).

  18. 18.

    Algra, A. M. & Rothwell, P. M. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 13, 518–527 (2012).

  19. 19.

    Cao, Y. et al. Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncol. 2, 762–769 (2016).

  20. 20.

    Green, J. et al. Menopausal hormone therapy and risk of gastrointestinal cancer: nested case-control study within a prospective cohort, and meta-analysis. Int. J. Cancer 130, 2387–2396 (2012).

  21. 21. Accessed 3 Jan 2018.

  22. 22.

    NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 390, 2627–2642 (2017).

  23. 23.

    Young, J. P. et al. Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review. J. Gastroenterol. Hepatol. 30, 6–13 (2015).

  24. 24.

    Hidayat, K., Yang, C. M. & Shi, B. M. Body fatness at an early age and risk of colorectal cancer. Int. J. Cancer 142, 729–740 (2018).

  25. 25.

    Ogino, S., Chan, A. T., Fuchs, C. S. & Giovannucci, E. Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field. Gut 60, 397–411 (2011).

  26. 26.

    Hughes, L. A. E., Simons, C. C. J. M., van den Brandt, P. A., van Engeland, M. & Weijenberg, M. P. Lifestyle, diet, and colorectal cancer risk according to (Epi)genetic instability: current evidence and future directions of molecular pathological epidemiology. Curr. Colorectal Cancer Rep. 13, 455–469 (2017).

  27. 27.

    Rescigno, T., Micolucci, L., Tecce, M. F., Capasso, A. Bioactive nutrients and nutrigenomics in age-related diseases. Molecules 22, pii: E105 (2017).

  28. 28.

    Slattery, M. L. et al. Infrequently expressed miRNAs in colorectal cancer tissue and tumor molecular phenotype. Mod. Pathol. 30, 1152–1169 (2017).

  29. 29.

    Ogino, S. et al. Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine. Gut 67, 1168–1180 (2018).

  30. 30.

    Carr, P. R. et al. Lifestyle factors and risk of sporadic colorectal cancer by microsatellite instability status: a systematic review and meta-analyses. Ann. Oncol. 29, 825–834 (2018).

  31. 31.

    Oosterhoff, M., Joore, M. & Ferreira, I. The effects of school-based lifestyle interventions on body mass index and blood pressure: a multivariate multilevel meta-analysis of randomized controlled trials. Obes. Rev. 17, 1131–1153 (2016).

  32. 32.

    Bibbins-Domingo, K. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. preventive services task force recommendation statement. Ann. Intern. Med. 164, 836–845 (2016).

  33. 33.

    Singh Ranger, G. The role of aspirin in colorectal cancer chemoprevention. Crit. Rev. Oncol. Hematol. 104, 87–90 (2016).

  34. 34.

    Marjoribanks, J., Farquhar, C., Roberts, H., Lethaby, A. & Lee, J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst. Rev. 1, Cd004143 (2017).

  35. 35.

    Gartlehner, G. et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: evidence report and systematic review for the US Preventive Services Task Force. JAMA 318, 2234–2249 (2017).

  36. 36.

    Brenner, H., Altenhofen, L., Stock, C. & Hoffmeister, M. Natural history of colorectal adenomas: birth cohort analysis among 3.6 million participants of screening colonoscopy. Cancer Epidemiol. Biomark. Prev. 22, 1043–1051 (2013).

  37. 37.

    Hewitson, P., Glasziou, P., Watson, E., Towler, B. & Irwig, L. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update. Am. J. Gastroenterol. 103, 1541–1549 (2008).

  38. 38.

    Scholefield, J. H., Moss, S. M., Mangham, C. M., Whynes, D. K. & Hardcastle, J. D. Nottingham trial of faecal occult blood testing for colorectal cancer: a 20-year follow-up. Gut 61, 1036–1040 (2012).

  39. 39.

    Shaukat, A. et al. Long-term mortality after screening for colorectal cancer. N. Engl. J. Med. 369, 1106–1114 (2013).

  40. 40.

    Hol, L. et al. Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy. Gut 59, 62–68 (2010).

  41. 41.

    Brenner, H. & Tao, S. Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur. J. Cancer 49, 3049–3054 (2013).

  42. 42.

    Robertson, D. J. et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US Multi-Society Task Force on colorectal cancer. Am. J. Gastroenterol. 112, 37–53 (2017).

  43. 43.

    Gies, A., Bhardwaj, M., Stock, C., Schrotz-King, P., Brenner, H. Quantitative fecal immunochemical tests for colorectal cancer screening. Int. J. Cancer 143, 234–244 (2018).

  44. 44.

    Rex, D. K. et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on colorectal cancer. Gastroenterology 153, 307–323 (2017).

  45. 45.

    Schreuders, E. H. et al. Colorectal cancer screening: a global overview of existing programmes. Gut 64, 1637–1649 (2015).

  46. 46.

    van der Vlugt, M. et al. Adherence to colorectal cancer screening: four rounds of faecal immunochemical test-based screening. Br. J. Cancer 116, 44–49 (2017).

  47. 47.

    Imperiale, T. F. et al. Multitarget stool DNA testing for colorectal-cancer screening. N. Engl. J. Med. 370, 1287–1297 (2014).

  48. 48.

    Brenner, H., Werner, S. & Chen, H. Multitarget stool DNA testing for colorectal-cancer screening. N. Engl. J. Med. 371, 184–185 (2014).

  49. 49.

    Brenner, H. & Chen, H. Fecal occult blood versus DNA testing: indirect comparison in a colorectal cancer screening population. Clin. Epidemiol. 9, 377–384 (2017).

  50. 50.

    Lin, J. S. et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 315, 2576–2594 (2016).

  51. 51.

    Atkin, W. et al. Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial. Lancet 389, 1299–1311 (2017).

  52. 52.

    Segnan, N. et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial—SCORE. J. Natl. Cancer Inst. 103, 1310–1322 (2011).

  53. 53.

    Holme, O. et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA 312, 606–615 (2014).

  54. 54.

    Schoen, R. E. et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N. Engl. J. Med. 366, 2345–2357 (2012).

  55. 55.

    Brenner, H., Stock, C. & Hoffmeister, M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies. BMJ 348, g2467 (2014).

  56. 56.

    Kaminski, M. F. et al. The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer. Endoscopy 44, 695–702 (2012).

  57. 57.

    Doubeni, C. A. et al. Effectiveness of screening colonoscopy in reducing the risk of death from right and left colon cancer: a large community-based study. Gut 67, 291–298 (2018).

  58. 58.

    Brenner, H., Stock, C. & Hoffmeister, M. In the era of widespread endoscopy use, randomized trials may strongly underestimate the effects of colorectal cancer screening. J. Clin. Epidemiol. 66, 1144–1150 (2013).

  59. 59.

    Chen, C., Stock, C., Hoffmeister, M. & Brenner, H. Public health impact of colonoscopy use on colorectal cancer mortality in Germany and the United States. Gastrointest. Endosc. 87, 213–221.e212 (2018).

  60. 60.

    Wolf, A. M. D. et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J. Clin. 68, 250–281 (2018).

  61. 61.

    Frampton, M. J. et al. Implications of polygenic risk for personalised colorectal cancer screening. Ann. Oncol. 27, 429–434 (2016).

  62. 62.

    Weigl, K. et al. Strongly enhanced colorectal cancer risk stratification by combining family history and genetic risk score. Clin. Epidemiol. 10, 143–152 (2018).

  63. 63.

    Jeon, J. et al. Determining risk of colorectal cancer and starting age of screening based on lifestyle, environmental, and genetic factors. Gastroenterology 154, 2152–2164.e19 (2018).

  64. 64.

    Weigl, K. et al. Genetic risk score is associated with prevalence of advanced neoplasms in a colorectal cancer screening population. Gastroenterology 155, 88–98.e10 (2018).

  65. 65.

    Lansdorp-Vogelaar, I., Knudsen, A. B. & Brenner, H. Cost-effectiveness of colorectal cancer screening. Epidemiol. Rev. 33, 88–100 (2011).

  66. 66.

    van Hees, F. et al. The value of models in informing resource allocation in colorectal cancer screening: the case of The Netherlands. Gut 64, 1985–1997 (2015).

  67. 67.

    Brenner, H., Altenhofen, L., Stock, C. & Hoffmeister, M. Prevention, early detection, and overdiagnosis of colorectal cancer within 10 years of screening colonoscopy in Germany. Clin. Gastroenterol. Hepatol. 13, 717–723 (2015).

  68. 68.

    Knudsen, A. B. et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA 315, 2595–2609 (2016).

  69. 69.

    Lew, J. B. et al. Long-term evaluation of benefits, harms, and cost-effectiveness of the National Bowel Cancer Screening Program in Australia: a modelling study. Lancet Public Health 2, e331–e340 (2017).

  70. 70.

    Walter, V., Jansen, L., Hoffmeister, M. & Brenner, H. Smoking and survival of colorectal cancer patients: systematic review and meta-analysis. Ann. Oncol. 25, 1517–1525 (2014).

  71. 71.

    Walter, V. et al. Smoking and survival of colorectal cancer patients: population-based study from Germany. Int. J. Cancer 137, 1433–1445 (2015).

  72. 72.

    Ordonez-Mena, J. M. et al. Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium. Ann. Oncol. 29, 472–483 (2018).

  73. 73.

    Walter, V. et al. Alcohol consumption and survival of colorectal cancer patients: a population-based study from Germany. Am. J. Clin. Nutr. 103, 1497–1506 (2016).

  74. 74.

    Sharma, A. et al. Tobacco smoking and postoperative outcomes after colorectal surgery. Ann. Surg. 258, 296–300 (2013).

  75. 75.

    Dinicola, S. et al. Nicotine increases survival in human colon cancer cells treated with chemotherapeutic drugs. Toxicol. Vitr. 27, 2256–2263 (2013).

  76. 76.

    Warren, G. W. et al. Nicotinic modulation of therapeutic response in vitro and in vivo. Int. J. Cancer 131, 2519–2527 (2012).

  77. 77.

    Vincenzi, B. et al. Cigarettes smoking habit may reduce benefit from cetuximab-based treatment in advanced colorectal cancer patients. Expert. Opin. Biol. Ther. 9, 945–949 (2009).

  78. 78.

    Cucina, A. et al. Nicotine stimulates proliferation and inhibits apoptosis in colon cancer cell lines through activation of survival pathways. J. Surg. Res. 178, 233–241 (2012).

  79. 79.

    Wei, P. L. et al. Nicotine enhances colon cancer cell migration by induction of fibronectin. Ann. Surg. Oncol. 18, 1782–1790 (2011).

  80. 80.

    Van Blarigan, E. L. & Meyerhardt, J. A. Role of physical activity and diet after colorectal cancer diagnosis. J. Clin. Oncol. 33, 1825–1834 (2015).

  81. 81.

    Otto, S. J. et al. Association of change in physical activity and body weight with quality of life and mortality in colorectal cancer: a systematic review and meta-analysis. Support. Care Cancer 23, 1237–1250 (2015).

  82. 82.

    Walter, V. et al. Physical activity and survival of colorectal cancer patients: Population-based study from Germany. Int. J. Cancer 140, 1985–1997 (2017).

  83. 83.

    Friedenreich, C. M., Shaw, E., Neilson, H. K. & Brenner, D. R. Epidemiology and biology of physical activity and cancer recurrence. J. Mol. Med. 95, 1029–1041 (2017).

  84. 84.

    Lee, J., Meyerhardt, J. A., Giovannucci, E. & Jeon, J. Y. Association between body mass index and prognosis of colorectal cancer: a meta-analysis of prospective cohort studies. PLoS One 10, e0120706 (2015).

  85. 85.

    Walter, V. et al. Prognostic relevance of prediagnostic weight loss and overweight at diagnosis in patients with colorectal cancer. Am. J. Clin. Nutr. 104, 1110–1120 (2016).

  86. 86.

    Carr, P. R. et al. Associations of red and processed meat with survival after colorectal cancer and differences according to timing of dietary assessment. Am. J. Clin. Nutr. 103, 192–200 (2016).

  87. 87.

    van Zutphen, M., Kampman, E., Giovannucci, E. L. & van Duijnhoven, F. J. B. Lifestyle after colorectal cancer diagnosis in relation to survival and recurrence: a review of the literature. Curr. Colorectal Cancer Rep. 13, 370–401 (2017).

  88. 88.

    Van Blarigan, E. L. et al. Association of survival with adherence to the American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors after colon cancer diagnosis: the CALGB 89803/Alliance trial. JAMA Oncol. 4, 783–790 (2018).

  89. 89.

    Li, P. et al. Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis. Gut 64, 1419–1425 (2015).

  90. 90.

    Sostres, C., Gargallo, C. J. & Lanas, A. Aspirin, cyclooxygenase inhibition and colorectal cancer. World J. Gastrointest. Pharmacol. Ther. 5, 40–49 (2014).

  91. 91.

    Frouws, M. A. et al. The mortality reducing effect of aspirin in colorectal cancer patients: Interpreting the evidence. Cancer Treat. Rev. 55, 120–127 (2017).

  92. 92.

    Coyle, C., Cafferty, F. H., Vale, C. & Langley, R. E. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Ann. Oncol. 27, 2184–2195 (2016).

  93. 93.

    Weberpals, J., Jansen, L., Carr, P. R., Hoffmeister, M. & Brenner, H. Beta blockers and cancer prognosis—The role of immortal time bias: a systematic review and meta-analysis. Cancer Treat. Rev. 47, 1–11 (2016).

  94. 94.

    Garland, C. F. & Gorham, E. D. Dose-response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: a meta-analysis. J. Steroid Biochem. Mol. Biol. 168, 1–8 (2017).

  95. 95.

    Zgaga, L. et al. Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer. J. Clin. Oncol. 32, 2430–2439 (2014).

  96. 96.

    Maalmi, H. et al. Relationship of very low serum 25-hydroxyvitamin D3 levels with long-term survival in a large cohort of colorectal cancer patients from Germany. Eur. J. Epidemiol. 32, 961–971 (2017).

  97. 97.

    Ng, K. et al. SUNSHINE: Randomized double-blind phase II trial of vitamin D supplementation in patients with previously untreated metastatic colorectal cancer. J. Clin. Oncol. 35(15_suppl), 3506 (2017).

  98. 98.

    Brenner, H., Jansen, L., Saum, K. U., Holleczek, B. & Schöttker, B. Vitamin D supplementation trials aimed at reducing mortality have much higher power when focusing on people with low serum 25-hydroxyvitamin D concentrations. J. Nutr. 147, 1325–1333 (2017).

  99. 99.

    World Cancer Research Fund, American Institute for Cancer Research. Continuous Update Project analysing research on cancer prevention and survival. Diet, nutrition, physical activity and colorectal cancer 2017. Accessed 16 Mar 2018.

  100. 100.

    The German Centre for Cancer Registry Data (ZfKD). Accessed 3 Feb 2018.

  101. 101.

    U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2014 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2017. Accessed 3 Feb 2018.

  102. 102.

    The Netherlands Comprehensive Cancer Organisation (IKNL). The Netherlands Cancer Registry. Accessed 3 Feb 2018.

  103. 103.

    Office for National Statistics (ONS). Cancer Registration Statistics, England. Accessed 3 Feb 2018.

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Author contributions

H.B. designed the review and drafted the review text, C.C. drafted the tables and figures and both authors contributed to revision and finalisation of the manuscript.

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  1. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

    • Hermann Brenner
    •  & Chen Chen
  2. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany

    • Hermann Brenner
  3. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

    • Hermann Brenner
  4. Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany

    • Chen Chen


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The authors declare that they have no competing interests.


The work of Chen Chen was supported by a scholarship from the German Cancer Research Center.


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Correspondence to Hermann Brenner.

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