Gastroenterology

Gastroenterology

Volume 118, Issue 5, May 2000, Pages 829-834
Gastroenterology

Alimentary Tract
Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer,☆☆

https://doi.org/10.1016/S0016-5085(00)70168-5Get rights and content

Abstract

Background & Aims: Identification of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome enables prevention of colorectal cancer (CRC) by means of colonoscopy and polypectomies. We evaluated the efficacy of screening in a controlled trial over 15 years. Methods: Incidence of CRC and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known. Results: CRC developed in 8 screened subjects (6%) compared with 19 control subjects (16 %; P = 0.014). The CRC rate was reduced by 62%. In mutation-positive subjects alone, the CRC rates were 18% in screened subjects and 41% in controls (P = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation status (40%). All CRCs in the study group were local, causing no deaths, compared with 9 deaths caused by CRC in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (P = 0.003), 4 vs. 12 in mutation-positive subjects (P = 0.05). Conclusions: Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.

GASTROENTEROLOGY 2000;118:829-834

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)

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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.

☆☆

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.

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