Insights of the prevalence of KRAS mutations in a real life population cohort of colorectal cancer based in north of Portugal

Colorectal cancer (CRC) is the third most common cancer worldwide, with 1.1 million new cases every year. In Portugal, recent data have shown that colorectal cancer was the most common cancer by incidence and the second by mortality. These age-standartized indexes are higher compared with neighbouring country Spain and have been attributed to an interplay of socio-demographic, lifestyle and environmental factors. In the era of precision medicine, treatment of advanced CRC includes anti-EGFR therapy. Resistance to these agents has been correlated with activating downstream mutations in KRAS, BRAF, and NRAS genes, leading to constitutive activation of the EGFR axis bypassing EGFR blockage. Therefore RAS mutations are an important predictive and prognostic marker. Little is known about patient and clinical factors associated with them. We studied the frequency and clinical characteristics in a real-world population of the North of Portugal.

This is a retrospective observational review of the patients with pathologically confirmed CRC or metastatic CRC followed at the Hospital Center of Trás-Os-Montes e Alto Douro from January to December 2017 to the present date. A total of 103 patients underwent KRAS, NRAS and BRAF mutations analysis using polymerase chain reaction (PCR) hybridization.

A cohort study of 103 patients with confirmed CRC, was constituted by 66 male (64,1%) and 37 female (35,9%) patients, with an average of 68,5 years of age. 48 (46,6%) out of 103 patients had positive KRAS mutation, namely in codons 12 (81,2%), 13 (10,4%), 146 (6,3%), 61 (2%). Of 25 CRC cases tested for NRAS mutation, 2 (8%) were positive for a mutation in codon 61. Tumors with KRAS mutations are equally prevalent in the right side (48,1%) and left side (45,5%) colon. Only 25,9% of the rectum tumors contain KRAS mutations. At the time of the diagnosis, a higher frequency of KRAS mutations was seen in patients with metastatic CRC (62,1%) compared with wild-type (WT) (37,9%). In the non-metastatic disease group, the frequency of KRAS mutations is lower (38,6% KRAS mutations vs 59,6% KRAS WT). At the initial disease stages (I-III), the average time for disease recurrence was 497 and 477 days for WT KRAS and KRAS mutated tumors, respectively.

This real-life retrospective study is the first to report the frequencies of KRAS gene mutations in the populations of the Trás-Os-Montes e Alto Douro, region of Portugal. The study revealed a high average KRAS mutation frequency in codon 12. It was also shown a higher prevalence of KRAS mutations in metastatic CRC compared with previously described.

The authors.

Has not received any funding.

All authors have declared no conflicts of interest.