| Objective:To study the influencing factors of adverse reactions after chemotherapy with cyclophosphamide combined with docetaxel in breast cancer patients,and to explore the correlation between ABCC4 and CYP2C9 gene polymorphism and adverse reactions to chemotherapy drugs,so as to provide evidence for the individualized treatment of breast cancer.Methods:A total of 154 han Chinese female breast cancer patients receiving postoperative chemotherapy in the department of breast surgery of zibo central hospital from December 2016 to December 2018 were selected in this study.The median age was 52.33 years old(18-70 years old).All breast cancer patients underwent modified radical mastectomy in our hospital,and the operation was completed by the deputy chief physician.In this study,the chemotherapy regimen was TC regimen,namely cyclophosphamide combined with docetaxel or paclitaxel liposome:75 mg·m2 docetaxel or 175 mg·m2 paclitaxel liposome+600 mg·m2 cyclophosphamide,with 21 days as a chemotherapy cycle,a total of 4 or 6 cycles.Fasting blood was collected from breast cancer patients on the third day after the end of the third cycle of chemotherapy,and the bone marrow suppression,liver and kidney function and other laboratory indicators of the patients were tested.The adverse reaction symptoms of chemotherapy patients were observed dynamically for 5 consecutive days.The source of the polymorphism test samples was divided into two groups,one group was non-breast cancer patients and the other group was breast cancer patients.Return samples of normal breast tissue,two groups of patients in the surgery patients of benign mammary gland pathological specimens in vitro 30 minutes from more than 1 cm,breast lesions of breast cancer patients with modified radical focal distance more than 5 cm to return the size of 0.3 cm3 normal breast tissue,collected by 2 ml cryopreserved tubes,in-178℃ preserved in liquid nitrogen.Eleven gene polymorphism detection sites were identified according to relevant literature and previous experimental studies.The polymorphisms of these genes were:ABCC4 rs1614102(A>G),rs9561778(T>G),rs4148532(T>G),rs1729775(G>G),rs1751070(G>C),rs7988595(C>A),rs870004(A>G),rs4771912(G>A),rs8001444(T>C)and CYP2C9 rs4918766(G>A),rs 1934968(T>0 C).Results:A total of 154 patients with breast cancer were included in this study,and no patients died or were lost to follow-up.All patients were breast cancer patients in central shandong.The age of onset of breast cancer patients was 30-65 years old,with an average age of 52.33 10.6 years.In 131 patients(131/154,85.06%),adverse reactions of varying degrees occurred during inpatient chemotherapy.The most common adverse reaction was myelosuppression(reduction of leukocytes,erythrocytes and platelets)in 108 patients(108/154,70.13%).In this study,univariate analysis was performed on the age,BMI,allergy history,depressive symptoms,pathological type and molecular typing of 154 patients enrolled in the study.There was a significant relationship between age,depressive symptoms and incidence of adverse reactions during chemotherapy hospitalization(P<0.05).There was no correlation between body mass index,pathological type and molecular analysis and adverse reactions of chemotherapy in breast cancer patients(P>0.05).Logistic multivariate regression analysis showed that age(OR=2.373,P=0.008)and depressive symptoms(OR=3.333,P=0.028)were independent predictors of adverse gastrointestinal reactions in breast cancer patients during chemotherapy.ABCC4 and CYP2C9 have a total of 11 polymorphic loci,and the distribution of these two genes can represent the distribution in the population.Nine with chi-square ABCC4 gene polymorphism loci and 2 gene polymorphism loci of CYP2C9 gene classification and correlation analysis between the incidence of adverse reactions,found that ABCC4 rs4148532(T>A)(X2=11.79,P=0.0006)and CYP2C9 rs4918766,(A)>G(X2=8.976,P=0.0027)gene polymorphism loci and there was A significant correlation between incidence of adverse reactions.Logistic multivariate regression analysis found that ABCC4 rs4148532 and CYP2C9 rs4918766 were independent predictors of myelosuppression in breast cancer TC chemotherapy regimen.ABCC4(rs4148532,A>T)showed that the risk of myelosuppressive adverse reaction with T allele was 5.51 times higher than that with A allele(OR=5.51,P=0.029).CYP2C9(rs4918766,G>A)was 5.683 times more likely to have A bone marrow suppression adverse reaction than was CYP2C9(OR=5.683,P=0.005).Therefore,the incidence of bone marrow suppression in patients with TC chemotherapy with AA genotype in ABBC4 and GG genotype in CYP2C9 was lower than that in patients with other genotypes.Conclusion:1.Age and depression during chemotherapy are the influencing factors of adverse reactions in breast cancer patients with chemotherapy,and are independent predictors of adverse reactions in the digestive system.2.The younger the breast cancer chemotherapy patients are or the more likely they are to have depressive symptoms during chemotherapy,the more likely they are to have adverse reactions in the digestive system.3.ABCC4(rs4148532)and CYP2C9(rs4918766)gene polymorphism are independent predictors of myelosuppressive adverse reactions caused by TC chemotherapy regimen,which is the genetic factor for the differences in chemotherapy drug tolerance between breast cancer chemotherapy patients. |
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