Cancer Risks in Lynch Syndrome, Lynch-like Syndrome, and Familial Colorectal Cancer Type X: a Prospective Cohort Study

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2020 May 26

PMID 32448342

Citations 24

Authors

Karolin Bucksch

Silke Zachariae

Stefan Aretz

Reinhard Buttner

Elke Holinski-Feder

Stefanie Holzapfel

Robert Huneburg

Matthias Kloor

Magnus von Knebel Doeberitz

Monika Morak

Gabriela Moslein

Jacob Nattermann

Claudia Perne

Nils Rahner

Wolff Schmiegel

Karsten Schulmann

Verena Steinke-Lange

Christian P Strassburg

Deepak B Vangala

Jurgen Weitz

Markus Loeffler

Christoph Engel

Affiliations

Soon will be listed here.

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.

Citing Articles

Genomic Medicine in the Developing World: Cancer Spectrum, Cumulative Risk and Survival Outcomes for Lynch Syndrome Variant Heterozygotes with Germline Pathogenic Variants in the and Genes.

Ndou L, Chambuso R, Algar U, Boutall A, Goldberg P, Ramesar R Biomedicines. 2025; 12(12.

PMID: 39767815 PMC: 11672899. DOI: 10.3390/biomedicines12122906.

Simplifying Mismatch Repair Deficiency Screening in Endometrial Adenocarcinoma: Immunohistochemistry with Two-Antibody Panel (PMS2 and MSH6).

Panyavaranant P, Pohthipornthawat N, Manchana T Asian Pac J Cancer Prev. 2024; 25(10):3667-3671.

PMID: 39471035 PMC: 11711341. DOI: 10.31557/APJCP.2024.25.10.3667.

Gynaecological cancer surveillance for women with Lynch syndrome: systematic review and cost-effectiveness evaluation.

Snowsill T, Coelho H, Morrish N, Briscoe S, Boddy K, Smith T Health Technol Assess. 2024; 28(41):1-228.

PMID: 39246007 PMC: 11403379. DOI: 10.3310/VBXX6307.

The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors.

Incorvaia L, Bazan Russo T, Gristina V, Perez A, Brando C, Mujacic C NPJ Precis Oncol. 2024; 8(1):190.

PMID: 39237751 PMC: 11377838. DOI: 10.1038/s41698-024-00672-0.

Human Leukocyte Antigen-Allelic Variations May Influence the Age at Cancer Diagnosis in Lynch Syndrome.

Ndou L, Chambuso R, Valley-Omar Z, Rebello G, Algar U, Goldberg P J Pers Med. 2024; 14(6).

PMID: 38929796 PMC: 11204704. DOI: 10.3390/jpm14060575.

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