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Purpose: Neurofibromatosis type 1 (NF1) is a complex, multisystem disorder that is characterized, among other features, by a higher risk of developing benign and malignant tumors. Despite NF1 being one of the most common autosomal dominant genetic disorders, data from adult individuals in several world regions remain elusive, including Hispanics. Methods: The present is a retrospective cohort study conducted among adult patients with a confirmed diagnosis of NF1 who attended a single cancer-reference center, the Instituto Nacional de Cancerologia in Mexico City from 2001 to 2021. Data were extracted from electronic health records and collected in an anonymous database by an NF1-expert physician in order to obtain demographic characteristics and detailed information regarding the development of tumors among this patient subgroup. All patients with malignant tumors or with benign tumors, which severely affected their quality of life, were included in this study. Results: Patient records were reviewed from 2001 to 2021. A total of N = 29 patients met the criteria, with a higher proportion of female compared with male subjects [N = 22 (75.9%) vs. N = 7 (24.1%)]. Patients had a mean age at diagnosis of tumors of 32.2 years (SD = 11.2 years). In terms of malignant neoplasms, the most frequent malignant tumor presented by patients in this cohort was malignant peripheral nerve sheath tumors (N = 7, 24.1%), this was followed by breast cancer (n = 4, 13.8% among all patients, 18.2% among female patients). Other tumors also identified in this cohort included melanoma, gastrointestinal stromal tumors, and rectal cancer. Conclusion: In Mexico, patients diagnosed with NF1 develop diverse tumors as adults. As described in other studies, the most frequent malignant tumor in this patient population is the malignant peripheral nerve sheath tumor. Further studies are required to increase the scarce information available for adult Hispanics with NF1. [ABSTRACT FROM AUTHOR]

Background: Individuals of Ashkenazi Jewish ancestry have been identified as having higher prevalence of specific pathogenic variants associated with susceptibility to specific rare and chronic diseases. In Mexico, the prevalence and composition of rare cancer predisposing germline variants in Ashkenazi Jewish individuals has not been evaluated. Aim and methods: We aimed to evaluate the prevalence of pathogenic variants by massive parallel sequencing in a panel of 143 cancer-predisposing genes in 341 women from the Ashkenazi Jewish community of Mexico, who were contacted and invited to participate in the study through the ALMA Foundation for Cancer Reconstruction. Pre- and posttest genetic counseling was given and a questionnaire on personal, gyneco-obstetric, demographic and lifestyle variables was conducted. From peripheral blood DNA, the complete coding region, and splicing sites of a panel of 143 cancer susceptibility genes, including 21 clinically relevant genes, were sequenced. The Mexican founder mutation BRCA1 ex9-12del [NC_000017.10(NM_007294):c. (825+1–826-1)_(4,589+1–4,590-1)del] was also evaluated. Results: Among study participants (mean age ±standard deviation: 47 ± 14) 15% reported a personal history of cancer (50/341). Fourteen percent of participants (48/ 341) were carriers of pathogenic and likely pathogenic variants distributed among seven high-risk genes (APC, CHEK2, MSH2, BMPR1A, MEN1, MLH1, and MSH6), whereas 18.2% (62/341) had variants of uncertain clinical significance in genes associated with breast and ovarian cancer susceptibility (list of genes with VUS). Pathogenic and likely pathogenic variants in 16 susceptibility genes with ambiguous or non-well-established risk association for cancer were detected in 17.6% (60/341) of participants. Sixty four percent of participants reported current alcohol consumption compared with the 39 percent prevalence of alcohol consumption in Mexican women. None of the participants carried the recurrent Ashkenazi and Mexican founder mutations in BRCA1 or BRCA2, but 2% (7/341) had pathogenic Ashkenazi Jewish founder variants in BLM. Conclusion: Our findings show a diverse pathogenic variant composition among the recruited individuals of Ashkenazi Jewish ancestry in Mexico consistent with being a high-risk population for genetic diseases, which warrants further investigation to adequately assess the burden of hereditary breast cancer in this group and implement appropriate preventative programs. [ABSTRACT FROM AUTHOR]