Cancer risks in the Lynch syndromes
Lynch syndrome is probably the most common inherited cancer susceptibility syndrome. Over the past decades, it has become apparent that this syndrome comprises a group of conditions caused by germline pathogenic variants (GPVs) in distinct DNA mismatch repair (MMR) genes, each associated with partia...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
23 February 2026
|
| In: |
Journal of the National Cancer Institute
Year: 2026, Pages: 1-3 |
| ISSN: | 1460-2105 |
| DOI: | 10.1093/jnci/djag029 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/jnci/djag029
|
| Author Notes: | William D. Foulkes, MBBS, PhD, and Aysel Ahadova, PhD |
| Summary: | Lynch syndrome is probably the most common inherited cancer susceptibility syndrome. Over the past decades, it has become apparent that this syndrome comprises a group of conditions caused by germline pathogenic variants (GPVs) in distinct DNA mismatch repair (MMR) genes, each associated with partially overlapping but distinguishable clinical features.1 The term “Lynch syndrome” was introduced in 1984 by C. Richard Boland,2 although Henry Lynch himself later favored the designation “hereditary non-polyposis colorectal cancer” despite early recognition that this label did not fully capture the tumor spectrum observed in affected families.3-5 Thus, Lynch had previously distinguished between site-specific colorectal cancer (CRC) (Lynch I) and CRC with extracolonic malignancies (Lynch II), accounting for the biological heterogeneity of the syndrome, so the notion that there is more than one Lynch syndrome has a long history.5-8 Identifying the responsible genes (MLH1, MSH2, MSH6, and PMS2) and the shared mechanism underpinning their action - MMR - led to a reversion to Boland’s original name8 and provided the current definition of Lynch syndrome as the presence of heterozygous GPVs in one of the MMR genes, including EPCAM deletions that silence MSH2.5,9 However, accumulating evidence indicates that substantial differences in cancer and adenoma risk,10,11 organ manifestations,10,12 and molecular as well as immunological characteristics of tumors11,13,14 exist between the heterozygotes for various MMR gene GPVs, highlighting the need for more precise risk stratification and tailored cancer prevention. |
|---|---|
| Item Description: | Gesehen am 18.03.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1460-2105 |
| DOI: | 10.1093/jnci/djag029 |