Unusual profile of germline genetic variants in unselected colorectal cancer patients from a high-prevalence region in Panama

The profile of germline genetic variants among colorectal cancer patients in Panama has not yet been explored. We recruited 95 patients with colorectal cancer in an Oncology Reference Hospital Unit in the Azuero region of central Panama, which exhibits the highest prevalence of colorectal cancer in Panama. DNA analysis was performed with a panel of 113 genes with germline mutations for cancer (TruSight(R) Cancer Sequencing Panel from Illumina). Among the 95 cases, 10 pathogenic/likely pathogenic variants (P/LP) were identified in the MUTYH, TP53, CHEK2, PALB2, ATM and BARD1 genes, representing 10% of the total. The median age of colorectal cancer onset in variant-positive cases was 71 years. The variant 1103G>A (p.Gly368Asp) in MUTYH was the most prevalent. The variant at c.1675_1676delCAinsTG (p.Gln559Ter) in PALB2 is new and is reported for the first time in this study. The genes where variants were most frequently detected were MUTYH (5 patients) and CHEK2 (2 patients). It is striking that in Panama, in this first cohort of 95 patients studied for genetic variants of susceptibility to colorectal cancer, we did not find any patient with mutations in mismatch repair (MMR), which in other cohorts around the world are the most frequently mutated genes found. This atypical genetic profile of germline genetic variants could be related to the unique mestizo characteristics of the population living in Azuero in the central region of Panama and could explain, in part, the high prevalence of colorectal cancer in its inhabitants.