1257P - Double heterozygous prevalence in hereditary cancer syndromes in Northern Mexico population

Background

Double heterozygous (DH) is a rare event, in DH patients, two pathogenic variants (PV) in two genes are present in the genomic DNA. Next-generation sequencing technologies with expanded gene, and affordable and more complete tools for diagnosis in hereditary cancer field, resulted in the identification of unexpected variants, including more than one variant in a single patient. The aim of this study was to identify the prevalence of double heterozygous and determine the effect of two pathogenic variants in hereditary cancer syndromes patients from Northeast Mexico.

Methods

This multicentric study included patients from the CECIL (The CUCC Early Cancer Detection Clinic) Hereditary Cancer Registry, and from the Hereditary Cancer Program from Tec Salud. Both centers accomplish patients of the Nuevo León state and adjacent states of Northern Mexico. Patients were recruited in a period of 7 years (from March of 2016 to March of 2023), a total of 872 patients were evaluated by Medical Geneticists and tested with NGS multigene cancer panel tests.

Results

A total of 294 (33.7%) patients had at least one PV, and 9 (3%) DH (two PV). Of all the DH patients, 8 (88.8%) had the clinical diagnosis of HBOC (Hereditary Breast Hereditary Cancer Syndrome), and one (11.1%) had Lynch Syndrome diagnosis. The mean age of cancer diagnosis was 42.8 years, compared with 40.3 mean for all the analyzed patients. None of the DH patients (0%) had synchronic or metachronic neoplasias diagnosed, compared to 19 (6.46%) with one PV patients. Among the identified variants BRCA1/2 and other homologous repair genes were found in 8 (88.8%) patients. The most frequent gene identified was MUTYH in 5 (55.5%) patients, surprisingly the variant c.1187G>A, known as a founder mutation in Northern Europe, was found in 4/5 (80%). These four Mexican patients had not known European ancestry.

Conclusions

This study suggest that the concurrence of two pathogenic variants did not impact the age of diagnosis or the risk of developing multiple neoplasia. variant c.1187G>A MUTYH founder mutation is frequent in our mestizo population and the most frequently found in the double heterozygous state.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Centro Universitario Contra el Cancer Hospital Dr Jose Eleuterio Gonzalez UANL. Centro de Cancer de Mama Hospital Zambrano Hellion Tec Salud.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.