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Genetics of Colorectal Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Introduction

Table 1. Estimated Relative and Absolute Risk of Developing Colorectal Cancer (CRC) continued...

(Refer to the Interventions/FAP section and the Chemoprevention in LS section in the Major Genetic Syndromes section of this summary for more information about chemoprevention.)

Modifying behavioral risk factors

Several components of diet and behavior have been suggested, with various levels of consistency, to be risk factors for CRC. (Refer to the PDQ summary on Prevention of Colorectal Cancer for more information.) These lifestyle factors may represent potential means of prevention.[78,80,81] Expert groups differ on the interpretation of the evidence for some of these components.

Little is known about whether these same factors are protective in people with a genetically increased risk of CRC. In one case-control study, low levels of physical activity, high caloric intake, and low vegetable intake were significantly related to cancer risk in people with no family history of CRC but showed no relationship in people with a family history, despite adequate statistical power to do so.[82]

References:

  1. American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed September 5, 2013.
  2. Burt RW, Petersen GM: Familial colorectal cancer: diagnosis and management. In: Young GP, Rozen P, Levin B, eds.: Prevention and Early Detection of Colorectal Cancer. London, England: WB Saunders, 1996, pp 171-194.
  3. Lynch HT, Smyrk T: Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review. Cancer 78 (6): 1149-67, 1996.
  4. Utsunomiya J, Lynch HT, eds.: Hereditary Colorectal Cancer: Proceedings of the Fourth International Symposium on Colorectal Cancer (ISCC-4) November 9-11, 1989, Kobe, Japan. Tokyo, Japan: Springer-Verlag, 1990.
  5. Herrera L, ed.: Familial Adenomatous Polyposis. New York, NY: Alan R. Liss Inc, 1990.
  6. Schoen RE: Families at risk for colorectal cancer: risk assessment and genetic testing. J Clin Gastroenterol 31 (2): 114-20, 2000.
  7. Howe JR, Mitros FA, Summers RW: The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol 5 (8): 751-6, 1998.
  8. Jeevaratnam P, Cottier DS, Browett PJ, et al.: Familial giant hyperplastic polyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome. J Pathol 179 (1): 20-5, 1996.
  9. Rashid A, Houlihan PS, Booker S, et al.: Phenotypic and molecular characteristics of hyperplastic polyposis. Gastroenterology 119 (2): 323-32, 2000.
  10. Neugut AI, Jacobson JS, DeVivo I: Epidemiology of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev 2 (2): 159-76, 1993 Mar-Apr.
  11. Shinya H, Wolff WI: Morphology, anatomic distribution and cancer potential of colonic polyps. Ann Surg 190 (6): 679-83, 1979.
  12. Fenoglio CM, Lane N: The anatomical precursor of colorectal carcinoma. Cancer 34 (3): suppl:819-23, 1974.
  13. Morson B: President's address. The polyp-cancer sequence in the large bowel. Proc R Soc Med 67 (6): 451-7, 1974.
  14. Muto T, Bussey HJ, Morson BC: The evolution of cancer of the colon and rectum. Cancer 36 (6): 2251-70, 1975.
  15. Stryker SJ, Wolff BG, Culp CE, et al.: Natural history of untreated colonic polyps. Gastroenterology 93 (5): 1009-13, 1987.
  16. O'Brien MJ, Winawer SJ, Zauber AG, et al.: The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. Gastroenterology 98 (2): 371-9, 1990.
  17. Winawer SJ, Stewart ET, Zauber AG, et al.: A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. National Polyp Study Work Group. N Engl J Med 342 (24): 1766-72, 2000.
  18. 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.
  19. Müller AD, Sonnenberg A: Prevention of colorectal cancer by flexible endoscopy and polypectomy. A case-control study of 32,702 veterans. Ann Intern Med 123 (12): 904-10, 1995.
  20. O'brien MJ, Winawer SJ, Zauber AG, et al.: Flat adenomas in the National Polyp Study: is there increased risk for high-grade dysplasia initially or during surveillance? Clin Gastroenterol Hepatol 2 (10): 905-11, 2004.
  21. Zauber AG, O'Brien MJ, Winawer SJ: On finding flat adenomas: is the search worth the gain? Gastroenterology 122 (3): 839-40, 2002.
  22. 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.
  23. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61 (5): 759-67, 1990.
  24. Vogelstein B, Kinzler KW: The multistep nature of cancer. Trends Genet 9 (4): 138-41, 1993.
  25. Lengauer C, Kinzler KW, Vogelstein B: Genetic instabilities in human cancers. Nature 396 (6712): 643-9, 1998.
  26. Vogelstein B, Fearon ER, Hamilton SR, et al.: Genetic alterations during colorectal-tumor development. N Engl J Med 319 (9): 525-32, 1988.
  27. Vogelstein B, Fearon ER, Kern SE, et al.: Allelotype of colorectal carcinomas. Science 244 (4901): 207-11, 1989.
  28. Kinzler KW, Vogelstein B: Landscaping the cancer terrain. Science 280 (5366): 1036-7, 1998.
  29. Lindblom A: Different mechanisms in the tumorigenesis of proximal and distal colon cancers. Curr Opin Oncol 13 (1): 63-9, 2001.
  30. Leggett B, Whitehall V: Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology 138 (6): 2088-100, 2010.
  31. Boland CR, Shin SK, Goel A: Promoter methylation in the genesis of gastrointestinal cancer. Yonsei Med J 50 (3): 309-21, 2009.
  32. Weisenberger DJ, Siegmund KD, Campan M, et al.: CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 38 (7): 787-93, 2006.
  33. Sjöblom T, Jones S, Wood LD, et al.: The consensus coding sequences of human breast and colorectal cancers. Science 314 (5797): 268-74, 2006.
  34. Kinzler KW, Vogelstein B: Colorectal tumors. In: Vogelstein B, Kinzler KW, eds.: The Genetic Basis of Human Cancer. 2nd ed. New York, NY: McGraw-Hill, 2002, pp 583-612.
  35. Woolf CM: A genetic study of carcinoma of the large intestine. Am J Hum Genet 10 (1): 42-7, 1958.
  36. Fuchs CS, Giovannucci EL, Colditz GA, et al.: A prospective study of family history and the risk of colorectal cancer. N Engl J Med 331 (25): 1669-74, 1994.
  37. Slattery ML, Kerber RA: Family history of cancer and colon cancer risk: the Utah Population Database. J Natl Cancer Inst 86 (21): 1618-26, 1994.
  38. Negri E, Braga C, La Vecchia C, et al.: Family history of cancer and risk of colorectal cancer in Italy. Br J Cancer 77 (1): 174-9, 1998.
  39. St John DJ, McDermott FT, Hopper JL, et al.: Cancer risk in relatives of patients with common colorectal cancer. Ann Intern Med 118 (10): 785-90, 1993.
  40. Duncan JL, Kyle J: Family incidence of carcinoma of the colon and rectum in north-east Scotland. Gut 23 (2): 169-71, 1982.
  41. Rozen P, Fireman Z, Figer A, et al.: Family history of colorectal cancer as a marker of potential malignancy within a screening program. Cancer 60 (2): 248-54, 1987.
  42. Hemminki K, Chen B: Familial association of colorectal adenocarcinoma with cancers at other sites. Eur J Cancer 40 (16): 2480-7, 2004.
  43. Houlston RS, Murday V, Harocopos C, et al.: Screening and genetic counselling for relatives of patients with colorectal cancer in a family cancer clinic. BMJ 301 (6748): 366-8, 1990 Aug 18-25.
  44. Johns LE, Houlston RS: A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol 96 (10): 2992-3003, 2001.
  45. Cottet V, Pariente A, Nalet B, et al.: Colonoscopic screening of first-degree relatives of patients with large adenomas: increased risk of colorectal tumors. Gastroenterology 133 (4): 1086-92, 2007.
  46. Winawer SJ, Zauber AG, Gerdes H, et al.: Risk of colorectal cancer in the families of patients with adenomatous polyps. National Polyp Study Workgroup. N Engl J Med 334 (2): 82-7, 1996.
  47. Ahsan H, Neugut AI, Garbowski GC, et al.: Family history of colorectal adenomatous polyps and increased risk for colorectal cancer. Ann Intern Med 128 (11): 900-5, 1998.
  48. Murff HJ, Peterson NB, Greevy R, et al.: Impact of patient age on family cancer history. Genet Med 8 (7): 438-42, 2006.
  49. Chen S, Wang W, Lee S, et al.: Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA 296 (12): 1479-87, 2006.
  50. Balmaña J, Stockwell DH, Steyerberg EW, et al.: Prediction of MLH1 and MSH2 mutations in Lynch syndrome. JAMA 296 (12): 1469-78, 2006.
  51. Barnetson RA, Tenesa A, Farrington SM, et al.: Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med 354 (26): 2751-63, 2006.
  52. Burt RW: Colon cancer screening. Gastroenterology 119 (3): 837-53, 2000.
  53. Kinzler KW, Nilbert MC, Su LK, et al.: Identification of FAP locus genes from chromosome 5q21. Science 253 (5020): 661-5, 1991.
  54. Groden J, Thliveris A, Samowitz W, et al.: Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66 (3): 589-600, 1991.
  55. Leppert M, Burt R, Hughes JP, et al.: Genetic analysis of an inherited predisposition to colon cancer in a family with a variable number of adenomatous polyps. N Engl J Med 322 (13): 904-8, 1990.
  56. Spirio L, Olschwang S, Groden J, et al.: Alleles of the APC gene: an attenuated form of familial polyposis. Cell 75 (5): 951-7, 1993.
  57. Brensinger JD, Laken SJ, Luce MC, et al.: Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. Gut 43 (4): 548-52, 1998.
  58. Soravia C, Berk T, Madlensky L, et al.: Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet 62 (6): 1290-301, 1998.
  59. Pedemonte S, Sciallero S, Gismondi V, et al.: Novel germline APC variants in patients with multiple adenomas. Genes Chromosomes Cancer 22 (4): 257-67, 1998.
  60. Sieber OM, Lamlum H, Crabtree MD, et al.: Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas. Proc Natl Acad Sci U S A 99 (5): 2954-8, 2002.
  61. Leach FS, Nicolaides NC, Papadopoulos N, et al.: Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75 (6): 1215-25, 1993.
  62. Papadopoulos N, Nicolaides NC, Wei YF, et al.: Mutation of a mutL homolog in hereditary colon cancer. Science 263 (5153): 1625-9, 1994.
  63. Nicolaides NC, Papadopoulos N, Liu B, et al.: Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 371 (6492): 75-80, 1994.
  64. Miyaki M, Konishi M, Tanaka K, et al.: Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet 17 (3): 271-2, 1997.
  65. Glanz K, Grove J, Le Marchand L, et al.: Underreporting of family history of colon cancer: correlates and implications. Cancer Epidemiol Biomarkers Prev 8 (7): 635-9, 1999.
  66. Winkels RM, Botma A, Van Duijnhoven FJ, et al.: Smoking increases the risk for colorectal adenomas in patients with Lynch syndrome. Gastroenterology 142 (2): 241-7, 2012.
  67. Järvinen HJ, Aarnio M, Mustonen H, et al.: Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118 (5): 829-34, 2000.
  68. Vasen HF, den Hartog Jager FC, Menko FH, et al.: Screening for hereditary non-polyposis colorectal cancer: a study of 22 kindreds in The Netherlands. Am J Med 86 (3): 278-81, 1989.
  69. Järvinen HJ, Mecklin JP, Sistonen P: Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 108 (5): 1405-11, 1995.
  70. Bülow S, Bülow C, Nielsen TF, et al.: Centralized registration, prophylactic examination, and treatment results in improved prognosis in familial adenomatous polyposis. Results from the Danish Polyposis Register. Scand J Gastroenterol 30 (10): 989-93, 1995.
  71. U.S. Preventive Services Task Force.: Guide to Clinical Preventive Services: Report of the U.S. Preventive Services Task Force. 2nd ed. Baltimore, Md: Williams & Wilkins, 1996.
  72. The periodic health examination. Canadian Task Force on the Periodic Health Examination. Can Med Assoc J 121 (9): 1193-254, 1979.
  73. Woolf SH: Screening for prostate cancer with prostate-specific antigen. An examination of the evidence. N Engl J Med 333 (21): 1401-5, 1995.
  74. Smith RA, Cokkinides V, Eyre HJ: American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin 56 (1): 11-25; quiz 49-50, 2006 Jan-Feb.
  75. Winawer S, Fletcher R, Rex D, et al.: Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 124 (2): 544-60, 2003.
  76. Church J, Simmang C; Standards Task Force., American Society of Colon and Rectal Surgeons.Collaborative Group of the Americas on Inherited Colorectal Cancer and the Standards Committee of The American Society of Colon and Rectal Surgeons., et al.: Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer). Dis Colon Rectum 46 (8): 1001-12, 2003.
  77. National Comprehensive Cancer Network.: NCCN Clinical Practice Guidelines in Oncology: Colorectal Cancer Screening. Version 1.2013. Rockledge, PA: National Comprehensive Cancer Network, 2013. Available online with free registration. Last accessed May 29, 2013.
  78. Tomeo CA, Colditz GA, Willett WC, et al.: Harvard Report on Cancer Prevention. Volume 3: prevention of colon cancer in the United States. Cancer Causes Control 10 (3): 167-80, 1999.
  79. Greenberg ER, Baron JA, Tosteson TD, et al.: A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N Engl J Med 331 (3): 141-7, 1994.
  80. Potter JD: Colorectal cancer: molecules and populations. J Natl Cancer Inst 91 (11): 916-32, 1999.
  81. Cummings JH, Bingham SA: Diet and the prevention of cancer. BMJ 317 (7173): 1636-40, 1998.
  82. La Vecchia C, Gallus S, Talamini R, et al.: Interaction between selected environmental factors and familial propensity for colon cancer. Eur J Cancer Prev 8 (2): 147-50, 1999.

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http:// cancer .gov or call 1-800-4-CANCER.

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Last Updated: September 04, 2014
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