Association Between Polymorphism Of HLA-DRB, DQB1 And Subsidiary-injury From Cancer Chemotherapy

Chemotherapy is a kind of therapeutic way that use chemicals to kill tumour cell, inhibit the growth and breeding of tumour cells, and promote the differentiation of tumour cells. It is the general therapeutic tool to produce a marked effect for primary lesion, metastasis and inferior clinical metastasis, and one of the most frequently using methods. Simultaneously chemotherapeutics secondary damage is serious, because it also kill normal tissue cells when it kill and wound tumour cells. Consequently it can result in damage for tissues and organs, and never cause patients to insist on the courses of treatment for the side effect of nausea, vomiting, diarrhea, debilitation, poor appetite, aleucocytosis and platelet degression. Its genesis and development concerned with many organs and tissues. At present the tumour chemotherapy adopt a method of standard chemotherapy. The method of selecting chemotherapeutics according to the position of tumorigenesis. Tumor exist heterogeneity in different patients, and often lead to patients conspicuous differences for sensibility of classic chems and toxico-side effect. For human beings, some chemotherapeutics have bene- ficial therapeutic effects and little toxico-side of effect; however, others have adverse therapeutic effect and heavy toxico-side effect for him. Even some medicines have fatal for some people. Standard chems exist a world of local, so it possess significant clinical purposes by guidance of pharmacogenomics and knowing individual gene differences-genetic polymorphism for developing drug treatment of tumor individuation。Genetic polymorphism is the hereditary basis of individual difference in medicine reactions, and provide the evidence for the individuallized treatment by recognizing the genic polymorphism and the relationship with the effect and the toxicity of medicine. With the researching in the medicine of chemical treatment on tumor, people have found that there are closed relation between the effect and the toxicity of the medicines and some genetic locus. The mechanism is that the chages of some locuses could result in the descent of the activity of the gene, which can control the metabolism of the medicines. But some changes of these can also make the gene lose its activity, then interfere the beginning of the metabolism of the medicines, even more, these could cause seriously toxicite adverse reactions. Such as DPD, which relate with the metabolism of the chemical treatment of tumor, is the major enzyme that participate the metabolism of pyrimidine, and also is the rate-limiting enzyme of the metabolism of 5-FU. The change from G to A on the 1st basic radical of the 14 thintron of the DPD gene, will cause the transmutation of the cut of mRNA, it can deactivate the enzyme, and then affect the metabolism of 5-FU, as the result, with the accumulation of the toxicity in the body, it will cause seriously toxicite diverse reactions. The people, whose DPD mutate, accept the treatment with 5-FU, will produce the diverse reaction and even dead. So ,if we detect the poly-genetic sites, and master the effect of the medicine in advance, and use the medicine aim to the chemical treatment directly, we will release the pain of the patient with tumor, and improve the quantity of their living, then increase the probability of existence under the proceed of the treatment. HLA is the major histocompatibility antigen, it is named as human leukocyte antigen because of its first expression in leukocyte, and named as HLA complex because of coding the gene group of HLA. It site on the 6th chromosome's short arm of human. It is the most complex genetic group with the most considerable polymorphism and mutle-gene, there are 224 gene sites and 1029 allelomorphes. There is the remarkable significance of the research of HLA, for example, there is relation between the specific type of HLA and the diseases, such as the abnormality expression of HLA-DRB1 and HLA-DQB1 could mediate the production and improvement of tumor. It is the most complicated heredity system of human, and also is the most geno-polymorphism. There are many differences in different race, different individuals and different tumors. But it is a blank of the report about the relation between the diverse reaction caused by the chemical treatment of tumor.Objective: To find the related g concom enes ofitant damage in tumor chemotherapy by the change of hematological and biochemical index of tumorous patient before and after chemotherapy and their correlation with the polymorphism of HLA-DRB1,DQB1.Method: We selected 24 malignant neoplastic patient (hepatoma, lung cancer, carcinoma of large intestine), excluding high blood pressure, diabetes, renal inadequacy, cardiac disease. The DNA of every patient were extracted and the polymorphism of their HLA- DRB1,DQB1 was detected by PCR-SSP. Meanwhile, each index before and after chemotherapy were detected, including hs-CRP,WBC,NEUT^#,LYM^#,MO^#,RBC,HGB,PLT,TBA,TBIL,DBIL,TP,ALB,ALT,AST,ALP,GGT,GLU,Urea,CR,UA,Ca²⁺,Mg²⁺,P³⁺,K⁺,Na⁺,Cl^-. All data were used to analyze the non-linear relationship between the change of every index before and after chemotherapy and the polymorphism of HLA-DRB1,DQB1 by SPSS13.0.Result: hs-CRP,WBC,NEUT^#,MO^#,TBIL,DBIL,ALT,AST,ALP,GGT,GLU,Urea,CR,Na⁺,Cl^- are more significant increase pre-chems than post-chems ; LYM^#,RBC,HGB,PLT,TBA,TP,ALB,UA,Ca²⁺,Mg²⁺,P³⁺are more significant decrease.There is correlation between the increase of Urea and HLA-DQB1*05; the increase of hs-CRP and HLA-DQB1*02; the increase of TBIL and HLA-DQB1*02; the increase of DBIL and HLA-DQB1*02; the decrease of TP and HLA-DQB1*02; the decrease of PLT and HLA-DQB1*02; the increase of PLT and HLA-DRB1*12; the decrease of TBA and HLA-DRB1*08; the increase of TBA and HLA-DRB1*15; the decrease of Ca²⁺ and HLA-DQB1*02; the decrease of Ca²⁺ and the two sets of HLA-DQB1*05 and HLA-DRB1*07; the increase of Cl^- and the two sets of HLA-DQB1*05 and HLA-DRB1*07; the increase of Na⁺ and HLA-DRB1*08; the increase of GGT and HLA-DRB1*15.Conclusion:1. Urea,hs-CRP,DBIL,TBIL,TP,PLT,TBA,Ca²⁺,Cl^-,Na⁺,GGT are the sensitive factors of chems damage, and there is correlation between them and the two sets of HLA-DQB1*02*05 and HLA-DRB1*07* 08*12*15. 2. Tumour chems have different affect on all sorts of laborartory test parameters,and perhaps it relate to genetic polymorphism of HLA.3. Tumour chems is perhaps marker gene of secondary impair of tumour chems.