Abstract
PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early onset of colorectal carcinomas (CRC). Recently, two HNPCC genes have been mapped and cloned, one in the short arm of chromosome 2 and another in the short arm of chromosome 3. There has been a major controversy about the frequency of HNPCC. The few estimates available have been based on series selected by age or series representing local area. The purpose of the present study was to design a nonselected, prospective, multicenter study, taking into account the family background and other risk factors of CRC. METHODS: The proportion of HNPCC of all (N=406) CRC cases was evaluated in a prospective multicenter study. Family history and other risk factors were investigated over a 12-month period for all new CRC patients in ten hospitals. These cases constituted 23 percent of all CRCs diagnosed in Finland during the study period. RESULTS: Three (0.7 percent) cases of verified and seven (1.7 percent) cases of suspected HNPCC were identified, following the evaluation of all families with features indicative of susceptibility to cancer. The proportion of identifiable risk factors of CRC was 5.8–7.5 percent (HNPCC, 0.7-2.4 percent; previous CRC, 3.4 percent; ulcerative colitis, 1.0 percent; familial adenomatous polyposis coli, 0.7 percent). CONCLUSION. This prospective multicenter study revealed that the frequency of hereditary colorectal cancer is lower than in some previous studies, when diagnosis is based on extensive pedigree analysis. This result with recent findings of common ancestral founding mutation in Finnish HNPCC families indicates that there may be geographic differences in the occurrence of HNPCC. However, this does not change the fact that identification of HNPCC—perhaps one of the most common inherited diseases identified in humans—has become a question of vital importance now when diagnosis of the syndrome and largescale screening of gene carriers using specific tests are on the horizon.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Lynch HT, Kimberling W, Albano WA,et al. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). Cancer 1985;56:934–8.
Mecklin J-P, Järvinen HJ. Tumor spectrum in cancer family syndrome (hereditary nonpolyposis colorectal cancer). Cancer 1991;68:1109–12.
Vasen HF, Offerhaus GJ, den Hertog-Jager FC,et al. The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in the Netherlands. Int J Cancer 1990;46:31–4.
Lynch HT, Lanspa SJ, Boman BM,et al. Hereditary nonpolyposis colorectal cancer: Lynch syndromes I and II. Gastroenterol Clin North Am 1988;17:679–712.
Vasen HF, Mecklin J-P, Meera Khan P, Lynch HT. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer (ICG-HNPCC) [Special communication]. Dis Col Rectum 1991;34:424–5.
Stephenson B, Finan PJ, Gascoyne J, Garbett F, Murday VA, Bishop DT. Frequency of familial colorectal cancer. Br J Surg 1991;78:1162–6.
Houlston RS, Collins A, Slack J, Morton NE. Dominant genes for colorectal cancer are not rare. Ann Hum Genet 1992;56:99–103.
Westlake PJ, Bryant HE, Huchcroft SA, Sutherland LR. Frequency of hereditary nonpolyposis colorectal cancer in Southern Alberta. Dig Dis Sci 1991;36:1441–7.
Kee F, Collins BJ. How prevalent is cancer family syndrome? Gut 1991;32:509–12.
Mecklin J-P. Frequency of hereditary nonpolyposis colorectal carcinoma. Gastroenterology 1987;93:1021–5.
Ponz de Leon M, Sassatelli R, Sacchetti C, Zanghieri G, Scalmati A, Roncucci L. Familial aggregation of tumors in the three-year experience of a population-based colorectal cancer registry. Cancer Res 1989;49:4344–8.
Peltomäki P, Aaltonen LA, Sistonen P,et al. Genetic mapping of a locus predisposing to human colorectal cancer. Science 1993;260:810–2.
Lindblom A, Tannegerd P, Novelius B, Nordenskjöld M. Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer. Nat Genet 1993;5:279–82.
Leach FS, Nicolaides NC, Papadopoulos N,et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 1993;75:1215–25.
Fishel R, Lescoe MK, Rao MR. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colorectal cancer. Cell 1993;75:1027–38.
Papadopoulos N, Nicolaides NC, Ying-Fei W,et al. Mutation of a mutL homolog in hereditary colon cancer. Science 1994;263:1625–9.
Bronner CE, Baker SM, Morrison PT,et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 1994:368:258–61.
Moller Jensen O, Carstensen B, Glattre E, Malker B, Pukkala E, Tulinius H. Atlas of cancer incidence in the Nordic Countries. Helsinki: Nordic Cancer Union, 1988.
Hakulinen T, Kenward M, Luostarinen T. Cancer in Finland in 1954–2008. Incidence, mortality and prevalence by region. Helsinki: Finnish Foundation for Cancer Research, 1989.
Järvinen HJ, Mecklin J-P, Sistonen P. Screening reduces colorectal cancer rate in hereditary nonpolyposis colorectal cancer (HNPCC) families. Gastroenterology (in press).
Nyström-Lahti M, Sistonen P, Mecklin J-P,et al. Close linkage to chromosome 3p and conservation of ancestral founding haplotype in hereditary nonpolyposis colorectal cancer families. Proc Natl Acad Sci USA 1994;91:6054–8.
Ponz de Leaon M, Sassatelli R, Benatti P, Roncucci L. Identification of hereditary nonpolyposis colorectal cancer in the general population. Cancer 1993;71:3493–501.
Aaltonen L, Sankila R, Mecklin J-P, Järvinen H, Peltomäki P, de la Chapelle A. A novel approach to estimate the proportion of hereditary nonpolyposis colorectal cancer of total colorectal cancer burden. Cancer Detect Prev 1994;18:57–63.
Järvinen HJ. Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival. Gut 1992;33:357–60.
Aaltonen LA, Peltomäki P, Leach FS,et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993;260:812–6.
Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993;260:816–9.
Ionov Y, Pernando MA, Malkhosyan S, Shibato D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993;363:558–61.
Marx J. New colon cancer gene discovered. Science 1993;200:751–2.
Steele Y Jr. Accomplishment and promise in the understanding and treatment of colorectal cancer. Lancet 1993;342:1092–6.
Author information
Authors and Affiliations
Additional information
Supported by grants from the Finnish Cancer Society, the Finnish Foundation for Gastroenterological Research, the Sigrid Juselius Foundation, and the Academy of Finland, Helsinki, Finland.
About this article
Cite this article
Mecklin, JP., Järvinen, H.J., Hakkiluoto, A. et al. Frequency of hereditary nonpolyposis colorectal cancer. Dis Colon Rectum 38, 588–593 (1995). https://doi.org/10.1007/BF02054116
Issue Date:
DOI: https://doi.org/10.1007/BF02054116