Incidence and Mortality
Definition of Prevention
Etiology and Pathogenesis of Colorectal Cancer

Incidence and Mortality

Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide [1] and the second leading cause of cancer deaths (irrespective of gender) in the United States.[2] It is estimated that there will be 148,810 new cases diagnosed in the United States in 2008 and 50,640 deaths due to this disease. Between 1998 and 2004, CRC incidence rates in the United States declined by 2.3% per year.[2] Over the past 20 years, the mortality rate has been declining. There was a 1.8% decline in mortality rate per year between 1985 and 2002. Between 2002 and 2004, the mortality rate declined by 4.7% per year.[2] The overall 5-year survival rate is 65.6%. About 6% of Americans are expected to develop the disease within their lifetimes.[3] The risk of CRC begins to increase after the age of 40 years and rises sharply at the ages of 50 to 55 years; the risk doubles with each succeeding decade, and continues to rise exponentially. Despite advances in surgical techniques and adjuvant therapy, there has been only a modest improvement in survival for patients who present with advanced neoplasms.[4,5] Hence, effective primary and secondary preventive approaches must be developed to reduce the morbidity and mortality from CRC.

Primary prevention involves the identification of genetic, biologic, and environmental factors that are etiologic or pathogenic in the development of cancer, and subsequent complete or significant interference with their effects on carcinogenesis. Removal of premalignant lesions (adenomas) may also be an effective form of primary prevention.

Genetics,[6,7] experimental,[8,9] and epidemiologic [10-12] studies suggest that CRC results from complex interactions between inherited susceptibility and environmental factors. It has been suggested that dietary factors may be responsible for a significant but poorly quantitated number of cancer cases.[13] Efforts to identify causes and develop effective preventive measures have led to the hypothesis that adenomatous polyps (adenomas) are precursors for the vast majority of CRCs.[14] While most of these adenomas are polypoid, flat and depressed lesions that may be more prevalent than previously recognized. Large flat and depressed lesions are more likely to be severely dysplastic. Specialized techniques may be needed to identify, biopsy, and remove such lesions.[15] In effect, measures that reduce the incidence and prevalence of adenomas may result in a subsequent decrease in the risk of CRC.[16] The finding of an adenoma on flexible sigmoidoscopy may warrant colonoscopy to evaluate the more proximal colon for synchronous neoplasms.[17] Many of the intervention trials employ adenoma recurrence or disappearance as a surrogate endpoint.[18] The evolution of a carcinoma from a small adenoma, however, takes many years.[10]

References

1. Shike M, Winawer SJ, Greenwald PH, et al.: Primary prevention of colorectal cancer. The WHO Collaborating Centre for the Prevention of Colorectal Cancer. Bull World Health Organ 68 (3): 377-85, 1990.  [PUBMED Abstract]
   
   
2. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008. 
   
   
3. Ries LAG, Eisner MP, Kosary CL, et al., eds.: SEER Cancer Statistics Review, 1975-2002. Bethesda, Md: National Cancer Institute, 2005. Also available online. Last accessed May 30, 2008. 
   
   
4. Moertel CG, Fleming TR, Macdonald JS, et al.: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322 (6): 352-8, 1990.  [PUBMED Abstract]
   
   
5. Krook JE, Moertel CG, Gunderson LL, et al.: Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324 (11): 709-15, 1991.  [PUBMED Abstract]
   
   
6. Willett W: The search for the causes of breast and colon cancer. Nature 338 (6214): 389-94, 1989.  [PUBMED Abstract]
   
   
7. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61 (5): 759-67, 1990.  [PUBMED Abstract]
   
   
8. Reddy B, Engle A, Katsifis S, et al.: Biochemical epidemiology of colon cancer: effect of types of dietary fiber on fecal mutagens, acid, and neutral sterols in healthy subjects. Cancer Res 49 (16): 4629-35, 1989.  [PUBMED Abstract]
   
   
9. Reddy BS, Tanaka T, Simi B: Effect of different levels of dietary trans fat or corn oil on azoxymethane-induced colon carcinogenesis in F344 rats. J Natl Cancer Inst 75 (4): 791-8, 1985.  [PUBMED Abstract]
   
   
10. Potter JD: Reconciling the epidemiology, physiology, and molecular biology of colon cancer. JAMA 268 (12): 1573-7, 1992 Sep 23-30.  [PUBMED Abstract]
    
    
11. Wynder EL, Reddy BS: Dietary fat and fiber and colon cancer. Semin Oncol 10 (3): 264-72, 1983.  [PUBMED Abstract]
    
    
12. Chen CD, Yen MF, Wang WM, et al.: A case-cohort study for the disease natural history of adenoma-carcinoma and de novo carcinoma and surveillance of colon and rectum after polypectomy: implication for efficacy of colonoscopy. Br J Cancer 88 (12): 1866-73, 2003.  [PUBMED Abstract]
    
    
13. Doll R, Peto R: The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 66 (6): 1191-308, 1981.  [PUBMED Abstract]
    
    
14. Hill MJ, Morson BC, Bussey HJ: Aetiology of adenoma--carcinoma sequence in large bowel. Lancet 1 (8058): 245-7, 1978.  [PUBMED Abstract]
    
    
15. Rembacken BJ, Fujii T, Cairns A, et al.: Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK. Lancet 355 (9211): 1211-4, 2000.  [PUBMED Abstract]
    
    
16. Winawer SJ, Zauber AG, Ho MN, et al.: Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 329 (27): 1977-81, 1993.  [PUBMED Abstract]
    
    
17. Read TE, Read JD, Butterly LF: Importance of adenomas 5 mm or less in diameter that are detected by sigmoidoscopy. N Engl J Med 336 (1): 8-12, 1997.  [PUBMED Abstract]
    
    
18. Vargas PA, Alberts DS: Colon cancer: the quest for prevention. Oncology (Huntingt) 7(11 suppl): 33-40, 1993. 
    
    

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