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. 2020 May 24;20(1):460.
doi: 10.1186/s12885-020-06926-x.

Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study

Karolin Bucksch  1 , Silke Zachariae  2 , Stefan Aretz  3   4 , Reinhard Büttner  5 , Elke Holinski-Feder  6   7 , Stefanie Holzapfel  3   4 , Robert Hüneburg  4   8 , Matthias Kloor  9   10 , Magnus von Knebel Doeberitz  9   10 , Monika Morak  6   7 , Gabriela Möslein  11 , Jacob Nattermann  4   8 , Claudia Perne  3   4 , Nils Rahner  12 , Wolff Schmiegel  13 , Karsten Schulmann  14   15 , Verena Steinke-Lange  6   7 , Christian P Strassburg  4   8 , Deepak B Vangala  13 , Jürgen Weitz  16 , Markus Loeffler  2 , Christoph Engel  2 ; German Consortium for Familial Intestinal Cancer
Affiliations

Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study

Karolin Bucksch et al. BMC Cancer. .

Abstract

Background: Individuals with pathogenic germline variants in DNA mismatch repair (MMR) genes are at increased risk of developing colorectal, endometrial and other cancers (Lynch syndrome, LS). While previous studies have extensively described cancer risks in LS, cancer risks in individuals from families without detectable MMR gene defects despite MMR deficiency (Lynch-like syndrome, LLS), and in individuals from families fulfilling the Amsterdam-II criteria without any signs of MMR deficiency (familial colorectal cancer type X, FCCX) are less well studied. The aim of this prospective study was to characterise the risk for different cancer types in LS, LLS, and FCCX, and to compare these with the cancer risks in the general population.

Methods: Data was taken from the registry of the German Consortium for Familial Intestinal Cancer, where individuals were followed up prospectively within the framework of an intensified surveillance programme at recommended annual examination intervals. A total of 1120 LS, 594 LLS, and 116 FCCX individuals were analysed. From this total sample, eight different cohorts were defined, in which age-dependent cumulative risks and standardised incidence ratios were calculated regarding the first incident occurrence of any, colorectal, stomach, small bowel, urothelial, female breast, ovarian, and endometrial cancer, separately for LS, LLS, and FCCX.

Results: The number of individuals at risk for first incident cancer ranged from 322 to 1102 in LS, 120 to 586 in LLS, and 40 to 116 in FCCX, depending on the cancer type of interest. For most cancer types, higher risks were observed in LS compared to LLS, FCCX, and the general population. Risks for any, colorectal, stomach, urothelial, and endometrial cancer were significantly higher in LLS compared to the general population. No significantly increased risks could be detected in FCCX compared to LLS patients, and the general population. Colorectal and endometrial cancer risks tended to be higher in LLS than in FCCX.

Conclusions: The characterisation of cancer risks in patients with LLS and FCCX is important to develop appropriate surveillance programmes for these specific intermediate risk groups. Larger prospective studies are needed to obtain more precise risk estimates.

Keywords: Cancer risk; Familial colorectal cancer type X; Lynch syndrome; Lynch-like syndrome; Prospective surveillance study.

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Conflict of interest statement

The authors declare that they have no competing interests. Matthias Kloor is an Editorial Board Member of BMC Cancer.

Figures

Fig. 1
Fig. 1
Age-dependent cumulative cancer risks
Fig. 2
Fig. 2
Age-dependent cumulative cancer risks of LS patients by gene
Fig. 3
Fig. 3
Comparison with general population risks: standardised incidence ratios (SIRs) with 95% confidence intervals
See this image and copyright information in PMC

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