Germline BRCA-Lynch syndrome MINAS: report of six Argentinian families and a systematic review of the literature.
Guillermo Alberto, Fernando Tortosa, María Dolores Mansilla Figueroa et al.
✦ AI-curated · Sources linked
In 30 seconds
This report combined six Argentinian families with a systematic review of 40 publications to describe the phenotype of BRCA-Lynch syndrome (BRCA-LS) MINAS. The analysis included 92 patients from 69 families. BRCA- and Lynch syndrome-related tumour patterns were represented in a balanced way, while tumours outside the established spectra were uncommon. Compared with carriers of MSH6 or PMS2 variants, carriers of MLH1 or MSH2/EPCAM variants had higher odds of multiple tumours (OR 3.60; 95% CI 1.29–10.55; p = 0.0095). The authors suggest that the two syndromes are generally expressed independently in clinically ascertained patients.
Key findings
- The combined analysis covered 92 patients from 69 families, including six newly reported Argentinian families and cases from 40 publications.
- BRCA- and Lynch syndrome-related tumour patterns were balanced; tumours outside the established BRCA or Lynch spectra were uncommon.
- MLH1 and MSH2/EPCAM variant carriers had higher odds of ≥ 2 tumors than MSH6 and PMS2 carriers (OR 3.60; 95% CI 1.29–10.55; p = 0.0095).
- MLH1 and MSH2/EPCAM variant carriers also had higher odds of extracolonic tumors (OR 3,28; CI95 1,26-8,84; p =0.0089).
Why it matters
Recognising the reported tumour patterns can help clinicians interpret cancer histories in people with pathogenic variants in both BRCA and mismatch repair genes. The findings support considering the established cancer spectra of each syndrome when assessing these patients, while cautioning against assuming that the variants interact synergistically. The observed differences by mismatch repair gene are consistent with known Lynch syndrome genotype–phenotype correlations.
What to keep in mind
The analysis concerns clinically ascertained patients with personal or family cancer histories; the authors state that systematically ascertained patients are needed to evaluate potential synergistic effects.