Pharmacogenetic profile associated with toxicity of fluoropyrimidines in colorectal cancer patients from Kazakhstan

Abstract

Abstract Background The differences in patients response to the same chemotherapy are one of the major problems in cancer treatment. Chemotherapy toxicity, including hematoxicity, can be life-threatening and makes a significant clinical problem. There is a lack of genetic data associated with toxicity of fluoropyrimidines in cancer patient from Kazakhstan. The aim of the study was to determine the genetic variation associated with toxicity in patients in Kazakhstan treated with fluoropyrimidines. Methods A total of 122 patients from Oncology hospital in Karaganda, Kazakhstan, diagnosed with colorectal cancer were recruited. Genotyping of 19 SNPs, associated with fluoropyrimidines toxicity, were performed by QuantStudio 12K Flex PCR and analyzed with Thermo Fisher Scientific Cloud service. Statistics were performed with R. Results 122 patients aged from 21 to 90 (female (n = 64), male (n = 58)) with rectum (33.61%), sigmoid (23.77%), ascending colon (9.02%), recto sigmoid (8.20%), cecum (7.38%), descending colon (5.74%), splenic flexure (3.28%), transverse colon (3.28%), anal (2.46%), diverticulum (1.64%), hepatic flexure (1.64%) cancer localization. rs41412545 (CC- 96.43%, CA-3.57%), rs55633228 (CC-96.74%, CT-3.26%), rs11636687 (CC-28.57%, TT-71.43%), rs12050587 (AA-100%), rs2231142 (GG-80%, GT-17%, TT-3%), rs225440 (TT-11.11%, TC-53.7%, CC-35.19%), rs2292997 (AA-2.56%, AG-23.08%, GG-74.36%), rs56022120 (CC-95.45%, CT-3.64%, TT-0.91%), rs56038477 (CC-100%), rs7194667 (GG-3.45%, GT-10.34%, TT-86.21%), rs148235907 (AA-0.95%, AG-3.81%, GG-95.24%), rs17376848 (AA-91.89%, AG-8.11%), rs79430272 (CC-95%, CT-2.5%, TT-2.5%), rs11479 (AA-2.88%, AG-26.92%, GG-70.19%), rs115457081 (AG-5%, GG-95%), rs1801133 (GG-45.83%, GA-45%, AA-9.17%), rs1801158 (CC-95.79%, CT-4.21%), rs3805945 (CC-1.8%, CT-16.22%, TT-81.98%), rs3918290 (CC-100%). Conclusion There is a high enough frequency of alleles (genotypes) associated with fluoropyrimidines toxicity in some polymorphisms.