Abstract 518P
Background
Screening for inherited susceptibility to cancer resulting from alterations in the mismatch repair (MMR) genes MLH1, MSH1, MSH2, MSH6 and PMS2 is recommended for all patients with Lynch Syndrome (LS)-related cancers. However, the genetic landscape of Guatemalan patients remains understudied compared to other Latin American countries. We aimed to identify and characterize patients with LS-related cancers at a national hospital in Guatemala.
Methods
Forty-five individuals meeting the National Comprehensive Cancer Network (NCCN) criteria for LS were analyzed using next-generation sequencing (NGS) in a two-year period, with a commercial 26-gene hereditary cancer panel. Variants were classified according to the guidelines of the American College of Medical Genetics and Genomics (ACMG) and ClinVar (NCBI).
Results
Out of the total (45), 22 patients (48.8%) were found to carry a variant classified as either of uncertain significance (VUS) or pathogenic (Table). Among these, 12 (26.6%) of them had a variant in MMR genes: MLH1 (11.1%), MSH2 (6.7%), MSH1 (2.2%), and MSH6 (6.7%). Notably, no variations were detected on the PMS2 gene. Additionally, variants in non-MMR genes were identified in 10 patients (22.2%). All 12 individuals with a variant in MMR genes had a family history of LS-related cancers, and the most prevalent types of variations were: splice donor (41.7%), missense (25.0%), nonsense (25.0%) and deletion (8.3%). Table: 518P
Clinical and genetic information of Guatemalan LS-related patients
| n | Percentage | MMR genes | ||||
| MLH1 | MSH2 | MSH1 | MSH6 | |||
| Type of cancer | ||||||
| Colorectal | 27 | 60.0 | 4 | 0 | 1 | 1 |
| Endometrial | 7 | 15.6 | 0 | 0 | 0 | 2 |
| Any LS-related ∗ | 11 | 24.4 | 1 | 3 | 0 | 0 |
| Total | 45 | 100.0 | 5 | 3 | 1 | 3 |
| Median age (years) | 45 | - | 47 | 45 | 37 | 49 |
| Sex | ||||||
| Male | 11 | 24.4 | 1 | 0 | 0 | 0 |
| Female | 34 | 75.6 | 4 | 3 | 1 | 3 |
| Family cancer history | ||||||
| Yes | 28 | 62.2 | 5 | 3 | 1 | 3 |
| No | 4 | 8.9 | 0 | 0 | 0 | 0 |
| Unknown | 13 | 28.9 | 0 | 0 | 0 | 0 |
∗Stomach, small bowel, ovary, pancreas, biliary tract
Conclusions
Despite the limited sample size, our results revealed that nearly half of the evaluated individuals harbored a VUS or pathogenic variant. These findings are consistent with those of other Latin American populations. Highlighting the importance of genetic screening in populations with a familial history of LS-related cancers, particularly in under-researched populations like Guatemala.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.