Molecular screening for hereditary nonpolyposis colorectal cancer: A prospective, population-based study

A. Percesepe, F. Borghi, M. Menigatti, L. Losi, M. Foroni, C. Di Gregorio, G. Rossi, M. Pedroni, E. Sala, F. Vaccina, L. Roncucci, P. Benatti, A. Viel, M. Genuardi, G. Marra, P. Kristo, P. Peltomäki, M. Ponz de Leon

Research output: Contribution to journalArticle

Abstract

Purpose: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. Patients and Methods: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. Results: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P <.01), high mucinous component (P <.01), and poor differentiation (P = .002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. Conclusion: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.

Original languageEnglish
Pages (from-to)3944-3950
Number of pages7
JournalJournal of Clinical Oncology
Volume19
Issue number19
Publication statusPublished - Oct 1 2001

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Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
Germ-Line Mutation
Colorectal Neoplasms
Incidence
Population
Microsatellite Repeats
DNA Mismatch Repair
Finland
Genetic Promoter Regions
Colonic Neoplasms
Methylation
Registries
Immunohistochemistry
Mutation
Genes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Percesepe, A., Borghi, F., Menigatti, M., Losi, L., Foroni, M., Di Gregorio, C., ... Ponz de Leon, M. (2001). Molecular screening for hereditary nonpolyposis colorectal cancer: A prospective, population-based study. Journal of Clinical Oncology, 19(19), 3944-3950.

Molecular screening for hereditary nonpolyposis colorectal cancer : A prospective, population-based study. / Percesepe, A.; Borghi, F.; Menigatti, M.; Losi, L.; Foroni, M.; Di Gregorio, C.; Rossi, G.; Pedroni, M.; Sala, E.; Vaccina, F.; Roncucci, L.; Benatti, P.; Viel, A.; Genuardi, M.; Marra, G.; Kristo, P.; Peltomäki, P.; Ponz de Leon, M.

In: Journal of Clinical Oncology, Vol. 19, No. 19, 01.10.2001, p. 3944-3950.

Research output: Contribution to journalArticle

Percesepe, A, Borghi, F, Menigatti, M, Losi, L, Foroni, M, Di Gregorio, C, Rossi, G, Pedroni, M, Sala, E, Vaccina, F, Roncucci, L, Benatti, P, Viel, A, Genuardi, M, Marra, G, Kristo, P, Peltomäki, P & Ponz de Leon, M 2001, 'Molecular screening for hereditary nonpolyposis colorectal cancer: A prospective, population-based study', Journal of Clinical Oncology, vol. 19, no. 19, pp. 3944-3950.
Percesepe A, Borghi F, Menigatti M, Losi L, Foroni M, Di Gregorio C et al. Molecular screening for hereditary nonpolyposis colorectal cancer: A prospective, population-based study. Journal of Clinical Oncology. 2001 Oct 1;19(19):3944-3950.
Percesepe, A. ; Borghi, F. ; Menigatti, M. ; Losi, L. ; Foroni, M. ; Di Gregorio, C. ; Rossi, G. ; Pedroni, M. ; Sala, E. ; Vaccina, F. ; Roncucci, L. ; Benatti, P. ; Viel, A. ; Genuardi, M. ; Marra, G. ; Kristo, P. ; Peltomäki, P. ; Ponz de Leon, M. / Molecular screening for hereditary nonpolyposis colorectal cancer : A prospective, population-based study. In: Journal of Clinical Oncology. 2001 ; Vol. 19, No. 19. pp. 3944-3950.
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title = "Molecular screening for hereditary nonpolyposis colorectal cancer: A prospective, population-based study",
abstract = "Purpose: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5{\%} and 13{\%} of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2{\%} to 2.7{\%} of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. Patients and Methods: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9{\%} of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. Results: Twenty-eight cases (8.3{\%} of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P <.01), high mucinous component (P <.01), and poor differentiation (P = .002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. Conclusion: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3{\%}] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.",
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T1 - Molecular screening for hereditary nonpolyposis colorectal cancer

T2 - A prospective, population-based study

AU - Percesepe, A.

AU - Borghi, F.

AU - Menigatti, M.

AU - Losi, L.

AU - Foroni, M.

AU - Di Gregorio, C.

AU - Rossi, G.

AU - Pedroni, M.

AU - Sala, E.

AU - Vaccina, F.

AU - Roncucci, L.

AU - Benatti, P.

AU - Viel, A.

AU - Genuardi, M.

AU - Marra, G.

AU - Kristo, P.

AU - Peltomäki, P.

AU - Ponz de Leon, M.

PY - 2001/10/1

Y1 - 2001/10/1

N2 - Purpose: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. Patients and Methods: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. Results: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P <.01), high mucinous component (P <.01), and poor differentiation (P = .002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. Conclusion: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.

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