ArticleHereditary cancer in clinical practice2024
Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated "Big Bang" pathway to CRC in three of the four Lynch syndromes.
Article in Hereditary cancer in clinical practice, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Trial
- Routes to colorectal cancer in Lynch syndrome: a decade of molecular and clinical insights converging on Schrödinger's cat.Familial cancer · 2026Review
- Fish Consumption and Colorectal Neoplasms among Lynch Syndrome Carriers.The Journal of nutrition · 2026Article
- Mutations Targeted by Nous-209 Immunotherapy Occur Early in Lynch Syndrome Carriers' Precancer Lesions with Microsatellite Instability.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Advances in Colorectal Cancer Cell Biology and Clonal Evolution.International journal of molecular sciences · 2026Review
- Adenomas and Beyond: Colonoscopy Surveillance, Racial and Socioeconomic Disparities in Lynch Syndrome.Gastro hep advances · 2026Article
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- Time to rethink colorectal cancer prevention strategies for lynch syndrome.Hereditary cancer in clinical practice · 2025Article
- Colorectal carcinogenesis in the Lynch syndromes and familial adenomatous polyposis: trigger events and downstream consequences.Hereditary cancer in clinical practice · 2025Review
- Colorectal Neoplasia Detection Rates in Lynch Syndrome.Cancers · 2024Article
- MSH6-proficient crypt foci in MSH6 constitutional mismatch repair deficiency: reversion of a frameshifted coding microsatellite to its wild-type sequence.Familial cancer · 2024Article
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Abstract
backgroundColorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. MATERIALS AND
methodsWe examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms.
resultsMost of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers.
conclusionsColonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports.
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