Identification of Germline Variants in Patients with Hereditary Cancer Syndromes in Northeast Mexico

Abstract

Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cancer. This research describes the implementation of a cancer prevention model, genetic counseling, and germline variants testing in an oncologic center in Mexico. A total of 315 patients received genetic counseling, genetic testing was offered, and 205 individuals were tested for HCS. In 6 years, 131 (63.90%) probands and 74 (36.09%) relatives were tested. Among the probands, we found that 85 (63.9%) had at least one germline variant. We identified founder mutations in BRCA1 and a novel variant in APC that led to the creation of an in-house detection process for the whole family. The most frequent syndrome was hereditary breast and ovarian cancer syndrome (HBOC) (41 cases with BRCA1 germline variants in most of the cases), followed by eight cases of hereditary non-polyposic cancer syndrome (HNPCC or Lynch syndrome) (with MLH1 as the primarily responsible gene), and other high cancer risk syndromes. Genetic counseling in HCS is still a global challenge. Multigene panels are an essential tool to detect the variants frequency. Our program has a high detection rate of probands with HCS and pathogenic variants (40%), compared with other reports that detect 10% in other populations.

Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population

“…Patients received face-to-face pre-test and post-test genetic counseling and laboratory reports from the leading geneticists (trained in oncogenetics) from each of the established hereditary cancer programs of Nuevo León México. Positive patients for genetic tests entered into an early detection and prevention program 10 .…”

“…It is well-known that the germline genetic cancer susceptibility is heterogeneous 6 . The prevalence and spectrum of GPVs in HBOC cancer patients may vary across ethnicities 5,[7][8][9][10] . According to the National Comprehensive Cancer Network (NCCN) guidelines, the genetic test now incorporates 17 non-BRCA genes (ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MSH2, MLH1, MSH6, NF1, PMS2, PALB2, PTEN, RAD51C, RAD51D, STK11, and TP53) for a comprehensive analysis of the patients [11][12][13] .…”