The importance of colon cancer (CC) increases due to the steady growth of morbidity and mortality from this disease in developed countries. According to the WHO, there are worldwide 600,000 new cases of CC yearly with half of them dying. This study aimed to improve the results of choosing personalized chemotherapy (CT) treatments by studying the molecular-genetic parameters of patients with CC.
We investigated samples of blood tests for gene polymorphisms XPD and DPYD_D949V, DPYD_14 in 75 patients with CC, who were treated at the departments of chemotherapy National Cancer Research Center of Uzbekistan in the period 2014-2016. The study included patients previously treated with several courses of CT containing 5-fluorouracil and platinum-based drugs and have acquired resistance to those regimens. Of the 75 patients: 35 women, 40 men. The median age was 39 ± 1. Patients with histological established mainly adenocarcinoma G2. Under the conditions of genetic laboratories we studied different variants of polymorphism alleles associated with the repair activity of the gene XPD.
The presence Lys751Gln polymorphism, Asp312Asn alleles in the XPD gene was found in 32 (43%) and 25 (33.3%) patients, respectively. Mutations in the genes DPYD_D949V, DPYD_14 were found in 29 (38.6%) patients from 75. As a result of the processing of retrospective data it was shown that in patients bearing polymorphisms and mutations in these genes the positive response to the therapy did not exceed 5%, and the relative risk of death among patients with mutant alleles was increased by 1.8 times (P = 0.030).
Thus, polymorphisms Lys751Gln, Asp312Asn XPD gene and gene DPYD is an important prognostic factor in the clinical application of CT with platinum drugs and 5-fluorouracil. The study of these factors can prevent inappropriate use of the different regimens of CT in the treatment of CC. Considering the pronounced incidence in certain groups of patients, these figures are subject to further additional study, and therefore a further study considering the toxicity of treatment, overall survival, and duration of the period without relapse is ongoing.
Clinical trial indentification
Legal entity responsible for the study
National Cancer Research Center of Uzbekistan
Health Ministry of Uzbekistan
All authors have declared no conflicts of interest.