Gastroenterology

Gastroenterology

Volume 130, Issue 7, June 2006, Pages 1995-2000
Gastroenterology

Clinical–alimentary tract
Prospective Results of Surveillance Colonoscopy in Dominant Familial Colorectal Cancer With and Without Lynch Syndrome

https://doi.org/10.1053/j.gastro.2006.03.018Get rights and content

Background & Aims: Lynch syndrome is an autosomal dominant predisposition to colorectal cancer caused by mutations in DNA mismatch repair genes; colorectal cancer risk is high. Few studies have addressed colorectal cancer risk in individuals from dominant families without mismatch repair deficiency. We sought to establish whether these individuals are also at increased risk by examining the incidence of advanced neoplasia during surveillance. Methods: In this prospective cohort study, BAT26 testing of tumors was carried out at 2 tertiary centers on 125 individuals from 97 families (with a dominant colorectal cancer history) to classify families as Lynch syndrome (microsatellite unstable) or non-Lynch syndrome (microsatellite stable). Colonoscopy results in 288 at-risk family members were compared. Results: Twenty-nine families were classified as Lynch syndrome and 68 as non-Lynch syndrome. Seven hundred seventy-six colonoscopies were undertaken. High-risk adenomas occurred in 7 of 91 (7.7%) Lynch syndrome individuals and 15 of 197 (7.6%) non-Lynch syndrome individuals, adjusted relative risk 1.15 (95% CI: 0.6–2.3). Cancer was observed only in Lynch syndrome individuals (4/91; 4.4%), Fisher exact test, P = .010. Multiple adenomas were only seen in non-Lynch syndrome individuals (13/197; 6.6%), Fisher exact text, P = .06. Conclusions: Individuals with an autosomal dominant family history of colorectal cancer with and without evidence of Lynch syndrome are at equal risk of high-risk adenomas during surveillance, but colorectal cancer was only seen in Lynch syndrome. Therefore non-Lynch syndrome individuals do require colonoscopic surveillance, but the interval could be lengthened because risk of (interval) cancer is low. Lynch syndrome individuals require short surveillance intervals as is the recommended practice.

Section snippets

Patient Selection

All families included in this study were registered with either the Cancer Research UK Family Cancer Clinic at St. Mark’s Hospital, London, United Kingdom, or The Netherlands Foundation for the Detection of Hereditary Tumours and were enrolled in colonoscopic surveillance. All families had a history suggestive of autosomal dominant pedigree inheritance of colorectal cancer. Families either fulfilled the Amsterdam Criteria I or II8, 9 or were classified as a dominant pattern pedigree family

BAT26 Analysis

Twenty-nine out of the 97 families tested exhibited MSI and were therefore classified as Lynch syndrome families (Table 1). The median (range) age at diagnosis of cancers tested was 44 (25–75) years in the Lynch syndrome group and 54 (18–82) years in the non-Lynch syndrome group. Only 3 of the 34 MSI tumors were from individuals aged 60 years or older.

Colonoscopy Findings

A total of 776 surveillance colonoscopies were carried out in first-degree relatives from 97 families. There were 288 individuals: 91 Lynch

Discussion

In this study, we prospectively evaluated the incidence of neoplasia during endoscopic surveillance in dominant families at risk of colorectal cancer with and without Lynch syndrome. We found that non-Lynch syndrome families (without MSI/mismatch repair [MMR] deficiency) when compared with Lynch syndrome families (with MSI/MMR deficiency) are actually at equal risk of developing high-risk adenomas but at significantly lower risk of developing (interval) cancers. Individuals from non-Lynch

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    2019, Gastrointestinal Endoscopy
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Supported by a NHS Research and Development Responsive Funding Grant and The Netherlands Organization for Health, Research, and Development: ZonMw.

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