Germline BRCA-Lynch syndrome MINAS: report of six Argentinian families and a systematic review of the literature
In brief
In 92 BRCA-Lynch carriers, cancers mostly matched the two syndromes
Across six newly reported families and published cases, cancer patterns were balanced between BRCA-related and Lynch syndrome tumors, while cancers outside those patterns were uncommon. Carriers with MLH1 or MSH2/EPCAM variants more often had multiple tumors and cancers outside the colon than those with MSH6 or PMS2 variants; whether the syndromes interact remains unclear because patients were clinically selected.
- Journal
- Familial cancer (Q2)
- Published
- 28 October 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Guillermo Alberto, Fernando Tortosa, María Dolores Mansilla Figueroa, Marina Antelo, Lucas Sebastian Sanchez, Gabriela Norese, et al.
- PMID
- 42955426
- DOI
- 10.1007/s10689-026-00615-7
Why clinicians should know about it
- Picked for Genetics (clinical) (top studies of the week, 1 November 2026): Germline BRCA and Lynch overlap informs hereditary cancer phenotype
Abstract
The co-occurrence of germline pathogenic or likely pathogenic variants (PVs) in BRCA1/BRCA2 and mismatch repair genes (Lynch Syndrome) (BRCA-LS) is an infrequent overlap of the two most frequent hereditary cancer syndromes. Recent reviews have examined whether the cancer risk profile in BRCA-LS carriers is independent for both syndromes or if both germline variants act as mutual modifying factors, including a synergistic effect. This study on BRCA-LS Multi-locus Inherited Neoplasia Allele Syndrome (MINAS) aims to report six affected families, perform a systematic review (SR) of the literature to identify previously reported patients, and analyze the phenotype of this genetic condition. Including the reported families and the patients retrieved by the SR (40 publications), 92 patients from 69 families were analyzed. The analysis of the BRCA-LS MINAS phenotype showed a balanced distribution of BRCA and LS-related tumor patterns and tumors outside the established BRCA or LS spectra were uncommon. Carriers of PVs in MLH1 and MSH2/EPCAM were more likely to be diagnosed with ≥ 2 tumors [OR 3.60-95% CI 1.29-10.55; p = 0.0095] and with extracolonic tumors [OR 3,28 (CI95 1,26-8,84) p =0.0089] than carriers of PVs in MSH6 and PMS2, findings that are consistent with known genotype-phenotype correlations in LS. Our findings suggest that in the context of clinically ascertained patients with a personal or family history of cancer, BRCA-LS MINAS is primarily characterized by the independent expression of both syndromes and that potential synergistic effects require further evaluation in studies including systematically ascertained patients.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.