Landscape of Multilocus Inherited Neoplasia Allele Syndrome in Mexican Population

Hereditary cancer syndromes (HCS) explain 5%-10% of all cancer cases. Patients with more than one germline pathogenic variant (GPV) result in a clinical syndrome known as multilocus inherited neoplasia allele syndrome (MINAS). In recent years, an increasing number of MINAS cases have been reported. This study aims to identify the prevalence of MINAS and determine the effect of two GPVs in HCS on patients from Northern Mexico.

Patients (N = 2,282) were recruited from four public oncology centers and two private institutions with hereditary cancer detection programs in Nuevo León, México. A medical geneticist collected all the patient's clinical data and gave genetic counseling. Patients with MINAS were detected using multigene panels to detect GPVs; findings were classified according to American College of Medical Genetics and Genomics guidelines. The genetic data of patients with MINAS were evaluated by their frequency and combination.

We found 386 (16.9%) patients with one or more variants and 23 (5.9%) MINAS patients (all females). The most frequent diagnosis was breast cancer (BC) in 20 (86.95%) cases, whereas 16 (69.56%) had triple-negative BC. We found 13 patients with BRCA1 GPVs (56.52%) as the most frequent, followed by MUTYH with five cases (21.73%). The combinations of BRCA1/CHEK2, BRCA1/CDKN2A, and BRCA1/BRCA2 were the most frequent. We found no atypical presentation in the cohort.

This is the first Mexican MINAS report and the largest Latin American cohort. We detected a higher prevalence of MINAS than other populations (5.9%). We found a tendency for additive phenotypical effect and, in some MINAS combinations, a modification in the age of diagnosis.