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Genetic factors and colorectal cancer in Ashkenazi Jews

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Abstract

The observed increased incidence of colorectal cancer in Ashkenazi Jews compared to other populations is unexplained but likely has a genetic component. The I1307K APC polymorphism/mutation is carried by 6--8% of Ashkenazim and increases the risk of colorectal cancer 1.5–2 fold. There are few differences between the phenotype of colorectal cancer in I1307K carriers and sporadic cases. It is estimated that the mutation accounts for 6% of cases of colorectal cancer in Jews of Eastern European heritage. It should not be the subject of mass screening in Ashkenazi Jews, although it may be important in cases of familial colorectal cancer. Even rarer is the 1906G→C MSH2 mutation carried by less than 1% of Ashkenazim, but as with other HNPCC mutations likely associated with a high risk of malignancy. Mutations at 15q13–14 are associated with the colorectal adenoma and carcinoma syndrome (CRAC) described in Ashkenazi families. The prevalence of the mutation is not known, nor its significance as a cause of colorectal cancer. Despite the paucity of genetic explanations for the high risk of colorectal cancer in Ashkenazim, that risk warrants aggressive colorectal cancer screening and particular attention to family history of malignancy in all Jews of Ashkenazi descent.

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References

  1. Rozen P, Lynch HT, Figer A et al. Familial colon cancer in the Tel-Aviv area and the influence of ethnic origin. Cancer 1987;60: 2355–9.

    Article  PubMed  CAS  Google Scholar 

  2. Modan B. Patterns of gastrointestinal neoplasia in Israel. Isr J Med Sci 1979;14:301–4.

    Google Scholar 

  3. Bat L, Pines A, Ron E et al. Colorectal adenomatous polyps and carcinoma in Ashkenazi and non-Ashkenazi Jews in Israel. Cancer 1986;58:1167–71.

    Article  PubMed  CAS  Google Scholar 

  4. Feldman GE. Do Ashkenazi Jews have a higher than expected cancer burden?Implications for cancer control prioritization efforts. Isr Med Assoc J 2001;3:341–6.

    PubMed  CAS  Google Scholar 

  5. Rozen P, Hellerstein SM, Horwitz C. The low incidence of colorectal cancer in a high risk population:its correlation with dietary habits. Cancer 1981;48:2692–5.

    Article  PubMed  CAS  Google Scholar 

  6. Greenwald P, Korns RF, Nasca PC, Wolfgang PE. Cancer in United States Jews. Cancer Res 1975;35:3507–12.

    PubMed  CAS  Google Scholar 

  7. Green MS. Differences between Israeli Jews and Arabs in mortality rates for diseases potentially associated with dietary risk factors. Public Health Rev 1998;26:31–40.

    PubMed  CAS  Google Scholar 

  8. Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996;87:159–70.

    Article  PubMed  CAS  Google Scholar 

  9. Houlston RS, Collins A, Slack J, Morton NE. Dominant genes for colorectal cancer are not rare. Ann Hum Genet 1992;56:99–103.

    Article  PubMed  CAS  Google Scholar 

  10. Cannon-Albright LA, Skolnick MH, Bishop DT et al. Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med 1988;319:533–7.

    Article  PubMed  CAS  Google Scholar 

  11. Groden J, Thliveris A, Samowitz W et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991;66:589–600.

    Article  PubMed  CAS  Google Scholar 

  12. Kinzler KW, Nilbert MC, Su LK et al. Identification of the FAP locus genes from chromosome 5q21.Science 1991;253:661–5.

    Article  PubMed  CAS  Google Scholar 

  13. Fodde R. The APC gene in colorectal cancer. Eur J Cancer 2002; 38:867–71.

    Article  PubMed  CAS  Google Scholar 

  14. Hampel H, Peltomaki P. Hereditary colorectal cancer:risk assessment and management. Clin Genet 2000;58:89–97.

    Article  PubMed  CAS  Google Scholar 

  15. Laken SJ, Petersen GME, Gruber SB et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat Genet 1997;17:79–83.

    Article  PubMed  CAS  Google Scholar 

  16. Gryfe R, Di Nicola N, Gallinger S, Redston M. Somatic instability of the APC I1307K allele in colorectal neoplasia. Cancer Res 1998; 58:4040–3.

    PubMed  CAS  Google Scholar 

  17. Prior TW, Chadwick RB, Papp AC et al. The I1307K polymor-phism of the APC gene in colorectal cancer. Gastroenterology 1999;116:58–63.

    Article  PubMed  CAS  Google Scholar 

  18. Zauber NP, Sabbath-Solitare M, Marotta SP, Bishop DT. The characterization of somatic APC mutations in colonic adenomas and carcinomas in Ashkenazi Jews with the APC I1307K variant using linkage disequilibrium. J Pathol 2003;199:149–51.

    Article  Google Scholar 

  19. Gryfe R, Di Nicola N, Lal G et al. Inherited colorectal polyposis and cancer risk of the APC I1307K polymorphism. Am J Hum Genet 1999;64:378–84.

    Article  PubMed  CAS  Google Scholar 

  20. Syngal S, Schrag D, Falchuk M et al. Phenotypic characteristics associated with the APC I1307K mutation in Ashkenazi Jewish patients with colorectal polyps. JAMA 2000;284:857–60.

    Article  PubMed  CAS  Google Scholar 

  21. Stern HS, Viertelhausen S, Hunter AGW et al. APC 1307K increases the risk of transition from polyp to colorectal carcinoma in Ashkenazi Jews. Gastroenterology 2001;120:392–400.

    Article  PubMed  CAS  Google Scholar 

  22. Calkins BM, Mendeloff AI. Epidemiology of inflammatory bowel disease. Epidemiol Rev 1986;8:60–91.

    PubMed  CAS  Google Scholar 

  23. Silverberg MS, Clelland C, Murphy JE et al. Carrier rate of APC I1307K is not increased in inflammatory bowel disease patients of Ashkenazi Jewish origin. Hum Genet 2001;108:205–10.

    Article  PubMed  CAS  Google Scholar 

  24. Woodage T, King SM, Wacholder S et al. The APC I1307K allele and cancer risk in a communty-based study of Ashkenazi Jews. Nat Genet 1998;20:62–5.

    Article  PubMed  CAS  Google Scholar 

  25. Frayling IM, Beck NE, Ilyas M et al. The APC variants I1307K and E1317Q are associated with colorectal tumors, but not always a family history. Proc Natl Acad Sci USA 1998;95:10722–7.

    Article  PubMed  CAS  Google Scholar 

  26. Drucker L, Shpilberg O, Neumann A et al. Adenomatous polyp-osis coli I1307K mutation in Jewish patients of different ethnicities. Cancer 2000;88:755–60.

    Article  PubMed  CAS  Google Scholar 

  27. Shtoyerman-Chen R, Friedman E, Figer A et al. The I307K APC polymorphism:prevalence in non-Ashkenazi Jews and evidence for a founder effect. Genet Test 2001;5:141–6.

    Article  PubMed  CAS  Google Scholar 

  28. Bahar AY, Taylor PJ, Andrews L et al. The frequency of founder mutations in the BRCA1, BRCA2 and APC genes in Australian Ashkenazi Jews.Cancer 2001;92:440–5.

    Article  PubMed  CAS  Google Scholar 

  29. Rozen P, Naiman T, Strul H et al. Clinical and screening implications of the I1307K adenomatous polposis coli gene variant in Israeli Ashkenazi Jews with familial colorectal neoplasia. Cancer 2002;94:2561–8.

    Article  PubMed  CAS  Google Scholar 

  30. Rozen P, Shomrat R, Strul H et al. Prevalence of the I1307K APC gene variant in Israeli Jews of differing ethnic origin and the risk for colorectal cancer. Gastroenterology 1999;116:54–7.

    Google Scholar 

  31. Strul H, Barenbolm E, Leshno M et al. The I1307K adenomatous polyposis coli gene variant does not contribute in the assesment of the risk for colorectal cancer in Ashkenazi Jews. Cancer Epidemiol Biomarkers Prev 2003;12:1012–5.

    PubMed  CAS  Google Scholar 

  32. Johnson KA, Rosenblum-Vos GM, Petersen JD et al. Colon cancer gene testing for APC I1307K in Ashkenazi Jews:the Hopkins experience. Proc 34th Annual Meeting of the American Society of Clinical Oncology, 1998;17:548a.

    Google Scholar 

  33. Lothe RA, Hektoen M, Johnsen H et al. The APC I1307K variant is rare in Norwegian patients with familial and sporadic colorectal or breast cancer.Cancer Res 1998;58:2923–4.

    PubMed  CAS  Google Scholar 

  34. Niell BL, Long JC, Rennert G, Gruber SB. Genetic anthropology of the colorectal-cancer susceptibility allele APC I1307K:evidence of genetic drift within the Ashkenazim. Am J Hum Genet 2003;73: 1250–60.

    Article  PubMed  CAS  Google Scholar 

  35. Risch N, Tang H, Kazenstein H, Ekstein J. Geographic distribution of disease mutations in the Ashkenazi Jewish population supports genetic drift over selection. Am J Hum Genet 2003;72:812–22.

    Article  PubMed  CAS  Google Scholar 

  36. Chen-Shtoyerman R, Theodor L, Harmati E et al. Genetic analysis of familial colorectal cancer in Israeli Arabs. Hum Mutat 2003;21: 446–7.

    Article  PubMed  Google Scholar 

  37. Figer A, Shtoyerman-Chen R, Tamir A et al. Phenotypic character-istics of colorectal cancer in I1307K APC germline mutation carriers compared with sporadic cases. Br J Cancer 2001;85:1368–71.

    Article  PubMed  CAS  Google Scholar 

  38. Locker G, Lynch H, Kaul K et al. The I1307k APC polymorphism in Ashkenazi Jews:association with familial colorectal cancer. Proc ASCO 2004 Gastrointestinal Cancers Symposium. San Francisco: American Society of Clinical Oncology, 2004;130.

    Google Scholar 

  39. Fidder H, Chen-Shtoyerman R, Barshack I et al. Immunohisto-chemical analysis of colon cancer in I1307K APc mutation carriers compared with non-carriers. Dig Dis Sci 2003;48:1102–5.

    Article  PubMed  CAS  Google Scholar 

  40. Gruber SB, Almog R, Low M, Rennert G. APC I1307K allele and the risk of hepatocellular carcinoma. Proc ASCO 1999;18.

  41. Houlston RS, Tomlinson IPM. Polymorphisms and colorectal tumor risk. Gastroenterology 2001;121:282–301.

    Article  PubMed  CAS  Google Scholar 

  42. Warthin AS. Heredity with reference to carcinoma. Arch Intern Med 1913;12:546–55.

    Google Scholar 

  43. Lynch HT, Shaw MW, Magnuson CW et al. Hereditary factors in cancer:study of two large Midwestern kindreds. Arch Intern Med 1966;117:206–12.

    Article  PubMed  CAS  Google Scholar 

  44. Lynch HT, de la Chapelle A. Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 1999;36:801–18.

    PubMed  CAS  Google Scholar 

  45. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome)proposed by the International Collaborative group on HNPCC. Gastroenterology 1999;116:1453–6.

    Article  PubMed  CAS  Google Scholar 

  46. Aaltonen LA, Salovaara R, Kristo P et al. Incidence of Hereditary Nonpolyposis Colorectal Cancer and the feasibility of molecular screening for the disease. N Engl J Med 1998;338:1481–7.

    Article  PubMed  CAS  Google Scholar 

  47. Rodriguez-Bigas MA, Boland CR, Hamilton SR et al. A National Cancer Institute workshop on hereditary nonpolyposis colorectal cancer syndrome:meeting highlights and Bethesda guidelines. J Natl Cancer Inst 1997;89:1758–62.

    Article  PubMed  CAS  Google Scholar 

  48. Yuan ZQ, Wong N, Foulkes WD et al. A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish HNPCC kindred:implications for clinical screening. J Med Genet 1999; 36:790–3.

    PubMed  CAS  Google Scholar 

  49. Marra G, D'Atri S, Yan H et al. Phenotypic analysis of hMSH2 mutations in mouse cells carrying human chromosomes. Cancer Res 2001;61:7719–21.

    PubMed  CAS  Google Scholar 

  50. Foulkes WD, Thiffault I, Gruber SB et al. The founder mutation MSH2*1906G! C is an important cause of hereditary nonpolyp-osis colorectal cancer in the Ashkenazi Jewish population. Am J Hum Genet 2002;71:1395–412.

    Article  PubMed  CAS  Google Scholar 

  51. Guillem JG, Rapaport BS, Kirchhoff T et al. A636P is associated with early-onset colon cancer in Ashkenazi Jews. J Am Coll Surg 2003;196:222–5.

    Article  PubMed  Google Scholar 

  52. Whitelaw SC, Murday VA, Tomlinson IPM et al. Clinical and molecular features of the hereditary mixed polyposis synrome. Gastroenterology 1997;112:327–34.

    Article  PubMed  CAS  Google Scholar 

  53. Thomas HJW, Whitelaw SC, Cottrell SE et al. Genetic mapping of the hereditary mixed polyposis syndrome to chromosome 6q.Am J Hum Genet 1996;58:770–6.

    PubMed  CAS  Google Scholar 

  54. Tomlinson I, Rahman N, Frayling I et al. Inherited susceptibility to colorectal adenomas and carinomas:evidence for a new predisposition gene on 15q14–q22.Gastroenterology 1999;116: 789–95.

    Article  PubMed  CAS  Google Scholar 

  55. Jaeger EEM, Woodford-Richens KL, Lockett M et al. An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13–q14 is associated with hereditary mixed polyposis syn-drome. Am J Hum Genet 2003;72:1261–7.

    Article  PubMed  CAS  Google Scholar 

  56. Lowy AM, Kordich JJ, Gismondi V et al. Numerous colonic adenomas in an individual with Bloom 's syndrome. Gastroenter-ology 2001;121:435–9.

    Article  CAS  Google Scholar 

  57. Li L, Eng C, Desnick R et al. Carrier frequency of the Bloom syndrome blmAsh mutation in the Ashkenazi Jewish population. Mol Genet Metab 1998;64:286–90.

    Article  PubMed  CAS  Google Scholar 

  58. Calin G, Herlea V, Barbanti-Brodano G, Negrini M. The coding region of the Bloom Syndrome BLM gene and of the CBL proto-oncogene is mutated in genetically unstable sporadic gastrointes-tinal tumors. Cancer Res 1998;58:3777–81.

    PubMed  CAS  Google Scholar 

  59. Goss KH, Risinger MA, Kordich JJ et al. Enhanced tumor formation in mice heterozygous for Blm mutation. Science 2002; 297:2051–3.

    Article  PubMed  Google Scholar 

  60. Gruber SB, Ellis NA, Scott KK et al. BLM heterozygosity and the risk of colorectal cancer. Science 2002;297:2013.

    Article  PubMed  CAS  Google Scholar 

  61. Cleary SP, Zhang W, Di Nicola N et al. Heterozygosity for BLM mutation and cancer risk. Cancer Res 2003;63:1769–71.

    PubMed  CAS  Google Scholar 

  62. Kedar-Barnes I, Baris H, Halpern PJ et al. The prevalence of breast and colorectal cancer among Ashkenazi Jewish Fanconi anemia and Bloom syndrome carriers. 2003 American Society of Human Genetics Meeting. Los Angeles, California, 2003.

    Google Scholar 

  63. Drucker L, Stackievitz R, Shpitz B, Yarkoni S. Incidence of BRCA1 and BRCA2 mutations in Ashkenazi colorectal cancer patients:preliminary study. Anticancer Res 2000;29:559–62.

    Google Scholar 

  64. Brose MS, Rebbeck TR, Calzone KA et al. Cancer risk estimate for BRCA1 mutation carriers identi ed in a risk evaluation program. J Natl Cancer Inst 2002;94:1365–72.

    PubMed  CAS  Google Scholar 

  65. Lin KM, Ternent CA, Adams DR et al. Colorectal cancer in hereditary breast cancer kindreds. Dis Colon Rectum 1999;42: 1041–5.

    Article  PubMed  CAS  Google Scholar 

  66. Niell BL, Rennert G, Bonner JD et al. BRCA1 and BRCA2 founder mutations and the risk of colorectal cancer. J Natl Cancer Inst 2004; 96:15–21.

    Article  PubMed  CAS  Google Scholar 

  67. Kirchoff T, Satagopan JM, Kauff ND et al. Frequency of BRCA1 and BRCA2 mutations in unselected Ashkenazi Jewish patients with colorectal cancer. J Natl Cancer Inst 2004;96: 68–70.

    Article  Google Scholar 

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Locker, G.Y., Lynch, H.T. Genetic factors and colorectal cancer in Ashkenazi Jews. Familial Cancer 3, 215–221 (2004). https://doi.org/10.1007/s10689-004-9547-x

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