Familial Cancer

, Volume 4, Issue 3, pp 233–237 | Cite as

The Incidence of Lynch Syndrome

  • Albert de la ChapelleEmail author


Lynch syndrome (LS) here is defined as carriership of a deleterious mismatch repair (MMR) gene mutation. By screening for MMR gene mutations in unselected colorectal or endometrial cancer patients, it was found that the prevalence of LS in colorectal and endometrial cancer patients is 1–3%. On extrapolation to the entire population, the incidence of LS is between 1:2000 and 1:660. As all screening methods are less than 100% sensitive, the above figures are underestimates.


frequency hereditary nonpolyposis colorectal cancer incidence Lynch syndrome mismatch repair gene mutations prevalence 


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  1. 1.
    Vasen, HFA, Mecklin, J-P, Khan, PM, Lynch, HT 1991The International Collaborative Group on Hereditary Non-polyposis Colorectal Cancer.Dis Colon Rectum344245CrossRefPubMedGoogle Scholar
  2. 2.
    Vasen, HFA, Watson, P, Mecklin, J-P, Lynch, HT, the, ICG-HNPCC 1999New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC.Gastroenterology11614536PubMedGoogle Scholar
  3. 3.
    Mecklin, JP 1987Frequency of hereditary colorectal carcinoma.Gastroenterology9310215PubMedGoogle Scholar
  4. 4.
    Ponz, Leon M, Sassatelli, R, Benatti, P, Roncucci, L 1993Identification of hereditary nonpolyposis colorectal cancer in the general population. The 6-year experience of a population-based registryCancer713493501PubMedGoogle Scholar
  5. 5.
    Mecklin, JP, Jarvinen, HJ, Hakkiluoto, A,  et al. 1995Frequency of hereditary nonpolyposis colorectal cancer. A prospective multicenter study in FinlandDis Colon Rectum3858893CrossRefPubMedGoogle Scholar
  6. 6.
    Lynch, HT, Lanspa, S, Smyrk, T,  et al. 1991Hereditary nonpolyposis colorectal cancer (Lynch syndromes I & II): genetics, pathology, natural history, and cancer control, part I.Cancer Genet Cytogenet5314360CrossRefPubMedGoogle Scholar
  7. 7.
    Westlake, PJ, Bryant, HE, Huchcroft, SA, Sutherland, LR 1991Frequency of hereditary nonpolyposis colorectal cancer in southern Alberta.Dig Dis Sci3614417CrossRefPubMedGoogle Scholar
  8. 8.
    Kee, F, Collins, BJ 1991How prevalent is cancer family syndrome?Gut3250912PubMedGoogle Scholar
  9. 9.
    Aaltonen, LA, Sankila, R, Mecklin, J-P,  et al. 1994A novel approach to estimate the proportion of hereditary nonpolyposis colorectal cancer of total colorectal cancer burden.Cancer Det Prev185763Google Scholar
  10. 10.
    Lynch, HT, Chapelle ,  A 2003Genomic medicine: Hereditary colon cancer.N Engl J Med34891932CrossRefPubMedGoogle Scholar
  11. 11.
    Wiesner, GL, Daley, D, Lewis, S,  et al. 2003A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2.PNAS100129615CrossRefPubMedGoogle Scholar
  12. 12.
    Laken, SJ, Petersen, GM, Gruber, SB,  et al. 1997Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC.Nat Genet177983CrossRefPubMedGoogle Scholar
  13. 13.
    Pasche, B, Kaklamani, V, Hou, N,  et al. 2004TBFBR1*6A and cancer: A meta-analysis of 12 case-control studies.J Clin Oncol227568CrossRefPubMedGoogle Scholar
  14. 14.
    Peltomäki, P, Vasen, HFA, The, International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer 1997Mutations predisposing to hereditary nonpolyposis colorectal cancer: Database and results of a collaborative study.Gastroenterology113114658PubMedGoogle Scholar
  15. 15.
    Cotton, RG, Scriver, CR 1998Proof of “disease causing” mutation.Hum Mut1213CrossRefPubMedGoogle Scholar
  16. 16.
    Syngal, S, Fox, EA, Li, C,  et al. 1999Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer. Implications for clinical predisposition testingJAMA28224753CrossRefPubMedGoogle Scholar
  17. 17.
    de, la Chapelle A 2004Genetic predisposition to colorectal cancer.Nat Rev Cancer476980CrossRefPubMedGoogle Scholar
  18. 18.
    Lipkin, SM, Rozek, LS, Rennert, G,  et al. 2004The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer.Nat Genet366949CrossRefPubMedGoogle Scholar
  19. 19.
    Suter, CM, Martin, DIK, Ward, RL 2004Germline epimutation of MLH1 in individuals with multiple cancers.Nat Genet36497501CrossRefPubMedGoogle Scholar
  20. 20.
    Terdiman, JP, Gum, JR, Conrad, PG,  et al. 2001Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing.Gastroenterology1202130CrossRefPubMedGoogle Scholar
  21. 21.
    Terdiman, JP, Levin, TR, Allen, BA,  et al. 2002Hereditary nonpolyposis colorectal cancer in young colorectal cancer patients: High-risk clinic versus population-based registry.Gastroenterology1229407CrossRefPubMedGoogle Scholar
  22. 22.
    Peel, DJ, Ziogas, A, Fox, EA,  et al. 2000Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases.J Natl Cancer Inst92151722CrossRefPubMedGoogle Scholar
  23. 23.
    Evans, DG, Wu, CL, Walsh, S,  et al. 2001Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases.J Natl Cancer Inst9371617CrossRefPubMedGoogle Scholar
  24. 24.
    Salovaara, R, Loukola, A, Kristo, P,  et al. 2000Population-based molecular detection of hereditary nonpolyposis colorectal cancer.J Clin Oncol1821932200PubMedGoogle Scholar
  25. 25.
    Aaltonen, LA, Salovaara, R, Kristo, P,  et al. 1998Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease.N Engl J Med338148187CrossRefPubMedGoogle Scholar
  26. 26.
    Cunningham, JM, Kim, C-Y, Christensen, ER,  et al. 2001The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas.Am J Hum Genet6978090CrossRefPubMedGoogle Scholar
  27. 27.
    Ravnik-Glavac, M., Potocnik, U, Glavac, D 2000Incidence of germline hMLH1 and hMSH2 mutations (HNPCC patients) among newly diagnosed colorectal cancers in a Slovenian population.J Med Genet375336Google Scholar
  28. 28.
    Percesepe, A, Borghi, F, Menigatti, M,  et al. 2001Molecular screening for hereditary nonpolyposis colorectal cancer: A prospective, population-based study.J Clin Oncol19394450PubMedGoogle Scholar
  29. 29.
    Samowitz, WS, Curtin, K, Lin, HH,  et al. 2001The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer.Gastroenterology1218308CrossRefPubMedGoogle Scholar
  30. 30.
    Goodfellow, PJ, Buttin, BM, Herzog, TJ,  et al. 2003Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers.Proc Natl Acad Sci USA100590813CrossRefPubMedGoogle Scholar
  31. 31.
    Ponz, Leon M, Sassatelli, R, Sacchetti, C, Zanghieri, G, Scalmati, A, Roncucci, L 1989Familial aggregation of tumors in the three-year experience of a population-based colorectal cancer registry.Cancer Res4943448PubMedGoogle Scholar
  32. 32.
    Nakagawa, H, Lockman, JC, Frankel, WL,  et al. 2004Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein but paralogous genes obscure mutation detection and interpretation.Cancer Res6447217PubMedGoogle Scholar
  33. 33.
    Adebamowo, CA, Adeyi, O, Pyatt, R,  et al. 2000Case report on hereditary non-polyposis colon cancer (HNPCC) in Nigeria.Afr J Med Med Sci297173PubMedGoogle Scholar
  34. 34.
    Boland, CR, Thibodeau, SN, Hamilton, SR,  et al. 1998A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial predisposition: Development of international criteria for the determination of microsatellite instability in colorectal cancer.Cancer Res58524857PubMedGoogle Scholar
  35. 35.
    Lindor, NM, Burgart, LJ, Leontovich, O,  et al. 2002Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors.J Clin Oncol2010438CrossRefPubMedGoogle Scholar
  36. 36.
    Chapelle,  A 2002Editorial.Microsatellite instability phenotype of tumors: genotyping or immunohistochemistry: The jury is still out. J Clin Oncol208979PubMedGoogle Scholar
  37. 37.
    Terdiman, JP 2001HNPCC: An uncommon but important diagnosis.Gastroenterology12110058PubMedGoogle Scholar
  38. 38.
    Järvinen, HJ, Aarnio, M, Mustonen, H,  et al. 2000Controlled 15-year trial on screening for colorectal cancer in hereditary nonpolyposis colorectal cancer families.Gastroenterology11882934PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Professor and Director, Human Cancer Genetics Program, Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA

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