Alimentary TractControlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer☆,☆☆
Section snippets
Subjects and examinations
The subjects consisted of 252 asymptomatic individuals, aged 20–66 years, belonging to 22 HNPCC families and being at 50% a priori risk to be mutation carriers. The inclusion criteria, selection of subjects to the study and control groups by free choice, and screening procedures have been described in detail previously.10 The final study group of 133 subjects had their first colonic examination between 1982 and 1986, whereas the 119 control subjects declined screening (78 subjects) or could not
Results
The number of subjects developing CRC was 8 (6%) of 133 in the study group compared with 19 (16%) of 119 in the control group (P = 0.014). The relative risk of CRC was 0.377 (95% confidence interval [CI], 0.171–0.829) in the study group vs. controls, corresponding to a reduction of 62% (95% CI, 17%–83%). Considering only known mutation-positive subjects, the frequencies of CRC were 18% (8 of 44) in the study group and 41% (19 of 46) in the controls (P = 0.02). The corresponding relative CRC
Discussion
The most important new finding of our extended screening trial was that colonoscopic screening and polypectomies not only reduce the incidence of CRC but also decrease the overall death rate by approximately 65%. This reduction was largely a result of the complete prevention of CRC deaths in the screened subjects compared with 9 deaths among 19 CRC cases in control subjects.
The survival advantage was statistically significant both between the original study groups and in the subgroups composed
Acknowledgements
The authors thank Dr. Annika Lindblom for the genetic testing of several subjects living in Sweden and Tuula Lehtinen, Kirsi Pylvänäinen, and Marjo Molin for organizing the screening, genetic testing, and data collection.
References (21)
- et al.
Lessons from the hereditary colorectal cancer
Cell
(1996) - et al.
The ICG on HNPCC. Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study
Gastroenterology
(1997) - et al.
Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis
Gastroenterology
(1996) - et al.
Hereditary nonpolyposis colorectal cancer: results of long-term surveillance in 50 families
Eur J Cancer
(1995) - et al.
Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer
Gastroenterology
(1995) - et al.
Hereditary non-polyposis colorectal cancer—morphologies, genes and mutations
Mutat Res
(1994) - et al.
Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review
Cancer
(1996) - et al.
Cancer risk in mutation carriers of DNA-mismatch-repair genes
Int J Cancer
(1999) Molecular mechanisms underlying hereditary nonpolyposis colorectal carcinoma
J Natl Cancer Inst
(1996)- et al.
Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer
Nat Genet
(1997)
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Address requests for reprints to: Heikki J. Järvinen, M.D., Second Department of Surgery, Helsinki University Central Hospital, P.O. Box 260, FIN-00029 HUCH, Helsinki, Finland. Fax: (358) 9-471-74675.
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Supported by grants from the National Institutes of Health (CA 67941 and CA 16058), European Union (BMH4-CT 96-0772), Foundation for Gastroenterological Research in Finland, the Sigrid Juselius Foundation, and the Finnish Cancer Foundation.