# Identification of Lynch syndrome among patients with colorectal cancer

Source: https://onco.cc/key-papers/paper-moreira-lynch-syndrome-identification-jama-2012/  
OnCo record `paper-moreira-lynch-syndrome-identification-jama-2012` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Pooling four large studies, over 10,000 people with bowel cancer, showed that testing every tumour finds every case of the commonest inherited bowel cancer syndrome, while the clinical rules then in use missed about one in eight.

## Summary

A pooled analysis of four cohorts of newly diagnosed colorectal cancer probands recruited between 1994 and 2010 (10,206 patients) examined personal, tumour-related and family characteristics alongside microsatellite instability, mismatch repair immunostaining and germline mutational status. Of 10,206 informative, unrelated probands, 312 (3.1%) were mismatch repair gene mutation carriers. In the population-based cohorts, universal tumour testing had sensitivity 100% and specificity 93.0%, against 87.8% sensitivity for the Bethesda guidelines, 85.4% for the Jerusalem recommendations and 95.1% for a selective strategy based on testing everyone diagnosed at 70 or younger plus older patients meeting the Bethesda guidelines. The selective strategy missed 4.9% of cases but required 34.8% fewer tumour tests and 28.6% fewer germline analyses.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: JAMA
- Year: 2012
- DOI: 10.1001/jama.2012.13088
- Authors: Moreira L, Balaguer F, Lindor N, et al.
- Findings: 312 of 10,206 probands (3.1%) carried a mismatch repair gene mutation.; Universal tumour testing: sensitivity 100%, specificity 93.0%.; Bethesda guidelines: sensitivity 87.8%; Jerusalem recommendations 85.4%.
- What it means: It is the evidence behind universal mismatch repair testing of every colorectal cancer, which is now standard in most guidelines and which, as a by-product, identifies everyone eligible for immunotherapy.
- Caveats: Pooled cohorts with differing ascertainment.; Universal testing costs more and finds variants of uncertain significance.; Germline analysis was not performed in every mismatch repair deficient case.

## Sources

- Moreira et al., JAMA 2012: identification of Lynch syndrome among 10,206 colorectal cancer probands: https://doi.org/10.1001/jama.2012.13088
- PubMed: https://pubmed.ncbi.nlm.nih.gov/23073952/

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [MSI and mismatch-repair testing](https://onco.cc/technologies/msi-mmr-testing/)
- targets: [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [MLH1](https://onco.cc/targets/mlh1/), [MSH2](https://onco.cc/targets/msh2/), [MSH6](https://onco.cc/targets/msh6/), [PMS2](https://onco.cc/targets/pms2/)
- institutions: [Hospital Clínic de Barcelona / IDIBAPS](https://onco.cc/institutions/hospital-clinic-barcelona/), [HUS Comprehensive Cancer Center, Helsinki University Hospital](https://onco.cc/institutions/helsinki-hus/), [Mayo Clinic](https://onco.cc/institutions/mayo-clinic/)
- pathways: [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/)
- terms: [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Lynch syndrome](https://onco.cc/terms/lynch-syndrome/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)
- journals: [JAMA](https://onco.cc/journals/jama/)
- trials: [NICHE-2](https://onco.cc/trials/niche-2/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [VENTANA MMR RxDx Panel](https://onco.cc/drugs/ventana-mmr-rxdx/)
- biomarkers: [dMMR (mismatch repair deficiency by IHC)](https://onco.cc/biomarkers/dmmr-ihc/), [MSI-high (microsatellite instability by PCR or sequencing)](https://onco.cc/biomarkers/msi-high/)

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