P-227 Comparative characteristics of somatic mutations in the KRAS gene in patients with colorectal cancer the South of Russia

Abstract

Introduction: Colorectal cancer (CRC) takes one of the leading places in the structure of cancer incidence and mortality in the world. Application of monoclonal antibodies to EGFR has increased the overall survival in patients with wild-type KRAS metastatic CRC. There are no studies on the frequency of KRAS mutations and their association with clinical and pathological features of patients with CRC in the South of Russia though this territory has its own population of particular qualities. The aim of the research was to study the polymorphism of SNP somatic mutations in KRAS gene in CRC-tumor biopsies taken from patients in the South of Russia.Methods: The study involved 800 patients of the South of Russia and the North Caucasus: 374 men and 426 women aged 28 to 89 years old with morphologically confirmed diagnosis of CRC. For molecular genetic studies 3 micron FFPE sections used, containing not less than 20% of tumor cells. Standard DNA extraction procedure included deparaffinization ortho-xylene lysis in 2% SDS - buffer with proteinase K and purification by column QIAamp® DNA FFPE Tissue Kit (QIAGENE, Germany). The set of reagents «Real-Time-PCR-KRAS-7M» («BioLink", Russia) were used to verify 7 missense mutations in 12 and 13 codons KRAS gene: G12C, G12S, G12R, G12V, G12D, G12A, G13D.Results: The overall incidence of mutations in KRAS gene was 38.6%. The mutations in men were found in 34.2%, in women - 42.4%. These differences were statistically significant for p = 0.017.Differences in the frequency of the mutant-type KRAS gene were also found in patients of the different age: younger than 55 years -33.9% and older than 55 years -41.02%. These differences were statistically significant for p = 0.052.The degree of adenocarcinoma differentiation was significant as well: G1-G2 -40.4% and G3 -27.9%. These differences were statistically significant for p = 0.01. Besides the stage was also significant for the incidence of the mutant-type KRAS gene: in 1-2 stages it was found in 29.3%, while in 3-4 stages -in 40.7%. These differences were statistically significant for p = 0.0095.Conclusion: The data discovered that the incidence of the mutant-type KRAS gene depends on gender, age, tumor differentiation and stage of the disease that could suggest the risk groups in population in the South of Russia. Introduction: Colorectal cancer (CRC) takes one of the leading places in the structure of cancer incidence and mortality in the world. Application of monoclonal antibodies to EGFR has increased the overall survival in patients with wild-type KRAS metastatic CRC. There are no studies on the frequency of KRAS mutations and their association with clinical and pathological features of patients with CRC in the South of Russia though this territory has its own population of particular qualities. The aim of the research was to study the polymorphism of SNP somatic mutations in KRAS gene in CRC-tumor biopsies taken from patients in the South of Russia. Methods: The study involved 800 patients of the South of Russia and the North Caucasus: 374 men and 426 women aged 28 to 89 years old with morphologically confirmed diagnosis of CRC. For molecular genetic studies 3 micron FFPE sections used, containing not less than 20% of tumor cells. Standard DNA extraction procedure included deparaffinization ortho-xylene lysis in 2% SDS - buffer with proteinase K and purification by column QIAamp® DNA FFPE Tissue Kit (QIAGENE, Germany). The set of reagents «Real-Time-PCR-KRAS-7M» («BioLink", Russia) were used to verify 7 missense mutations in 12 and 13 codons KRAS gene: G12C, G12S, G12R, G12V, G12D, G12A, G13D. Results: The overall incidence of mutations in KRAS gene was 38.6%. The mutations in men were found in 34.2%, in women - 42.4%. These differences were statistically significant for p = 0.017.Differences in the frequency of the mutant-type KRAS gene were also found in patients of the different age: younger than 55 years -33.9% and older than 55 years -41.02%. These differences were statistically significant for p = 0.052.The degree of adenocarcinoma differentiation was significant as well: G1-G2 -40.4% and G3 -27.9%. These differences were statistically significant for p = 0.01. Besides the stage was also significant for the incidence of the mutant-type KRAS gene: in 1-2 stages it was found in 29.3%, while in 3-4 stages -in 40.7%. These differences were statistically significant for p = 0.0095. Conclusion: The data discovered that the incidence of the mutant-type KRAS gene depends on gender, age, tumor differentiation and stage of the disease that could suggest the risk groups in population in the South of Russia.