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.

Keywords: genetic counseling; hereditary cancer syndromes; pathogenic variants.

Figure 1

Flowchart of genetic counseling: of the total population (n = 3283), 315 patients were candidates for genetic testing.

Figure 2

HCS frequency: Distribution of the variants in probands and relatives and their diagnosis. One proband was a double heterozygous for hereditary paraganglioma-pheochromocytoma (PGL/PCC) and DICER1 cancer predisposition (DICER1 CP) syndrome. FAP, HDGC: hereditary diffuse gastric cancer syndrome, HMPC: hereditary melanoma-pancreas cancer predisposition syndrome, PGL/PCC.