P-265 The study of mutations of the KRAS, NRAS, and BRAF genes in patients with colorectal cancer depending on gender, age, race in the population of the Republic of Kazakhstan

Abstract

Of 3218 patients with colorectal cancer (CRC) who were registered in the Republic of Kazakhstan in 2018, 1476 have died. In the structure of mortality, colorectal cancer is ranked 4th. Recently, studies of the frequency of the KRAS gene mutation and analysis of its correlation with the clinical course of CRC have been conducted in different countries. The relationship of sex, age, race, and localization of the primary tumor to the status of the KRAS, NRAS, and BRAF genes in CRC remains the subject of discussion. The research material was paraffin blocks of the primary tumor of patients with CRC (n = 332). Using genomic DNA, real-time PCR revealed the most common mutations: the KRAS gene (exon 2, 3, 4), the NRAS gene (in codons 12,13, 61,146), V600E of the BRAF gene. For the first time, the occurrence of mutations in the KRAS and NRAS genes (42.5% and 2.4%), which is equivalent to the international (∼ 40%), was determined, and 183 (55.1%) patients were of the wild type. Mutation of the BRAF gene occurred in 9.3% of cases, and all of them had unmutated RAS status. The frequency of mutations among women and men was the same and was more often observed in the G12D codon. An analysis of the dependence of the type of mutation on gender did not show significant differences, however, there was a tendency to an increase in the frequency of mutations in women. For a pair of “female KRAS mutations,” the value of the correlation coefficient was rp = 0.04, p = 0.06. An analysis of the relationship between mutations and race revealed the predominance of the wild type in the Asian group - 94 (51.4%), in Europeans the KRAS gene mutation was more often detected - 81 (54.4%) patients. When studying the occurrence of mutations in two age groups (group 1 - from 25 to 59, 2 - from 60 to 89 years), it was found that patients of group 2 were more likely to have a mutated type of RAS genes, and group 1 was significantly more likely to have a wild type. In the study, gene mutations were more common with primary tumor localization in the right compared to the left (p = 0.001). There was a tendency towards increase in the number of gene mutations with an increase in the frequency of damage to the distal colon and especially the rectum. The obtained results point to the need to continue research on the comprehensive study and identification of molecular genetic characteristics of CRC. With a more in-depth analysis of the relationship of mutations, it is possible to achieve improved therapy results and increase prospects for long-term survival.