Correlation Between DNA Repair Rates And Platinum-containing Chemotherapy Efficacy For Patients With Advanced Gastrointestinal Cancer

Background & Objective: About 98% of digestive system tumor are malignant, and the digestive tract cancer and esophageal cancer, gastric cancer and colorectal cancer are the most common, and in recent years they has shown a growth in trend. Chemotherapy is an important part of the comprehensive treatment for malignant tumor at present. Treatment containing cisplatin or oxaliplatin scheme applied in advanced digestive tract tumors has generally been recognized. However, chemotherapy also have great disadvantage, it lacks selective inhibitory action on tumor cells and potential systemic toxicity. For patients with advanced malignant tumor, antitumor chemotherapy itself caused the decline in the quality of life is not to be neglected. Therefore, patients can be treated in pre detection are more likely to benefit patients with chemical treatment, not only can it improve the curative effect and evaluation of prognosis of chemotherapy, but also it can avoid inappropriate treatment bring patient the burden of life.Chemotherapy for patients can cause cells of the body to start the repair mechanisms thus influencing of platinum based chemotherapy sensitivity. The individual differences also determines the DNA repair capacity of different degree response to chemotherapy effect. Related genes, enzymes and proteins involved in DNA damage repair at present only play minimal role in DNA repair mechanism, thus not enough to support the realization of individual chemotherapy and theoretical basis for prediction of short-term curative effect. The rate of repair of DNA(DNA repair rate, DRR) can reflect the individual DNA repair capacity, thus can be implemented as individual chemotherapy and prediction of an important basis for the recent curative effect.Therefore, this study use single cell gel electrophoresis(single cell gel electrophoresis, SCGE) to detect PBLC DRR of gastrointestinal tumor patients with initial treatment combined with the clinical evaluation of platinum containing chemotherapy regimens for correlation studies, in order to provide the basis of advanced digestive tract malignant tumor patient evaluation and prognosis prediction of chemotherapy.Methods The DRR of PBLC from 112 patients with advanced gastrointestinal cancer patients(tumor group)were detected by single cell gel electrophoresis(SCGE),and the other 60 patients with healthy subjects were selected as controls(control group).Cancer patients were treated in parallel platinum-containing chemotherapy regimens to evaluate the short-term effect. Analyze the DRR of the two platinum groups before and after exposure repair to platinum and DRR of cancer group and determine the correlation between clinical pathological features and efficacy of chemotherapy regimens containing platinum.Results Tail length and tail-phase were utilized to detect the esophageal cancer(Z=-4.687 P=0.000, Z=-4.939 P=0.000),gastric cancer(Z=-5.473 P=0.000, Z=-3.789 P=0.OOO) and colorectal cancer(Z=-5.796 P=O.OOO, Z=-5.206 P=0.000),the resulting PBLC DRR of cancer group were lower than the control group counterpart. The PBLC DRR of tumor group exhibit no correlation to sex, age, ECOG score, alcohol habits and tissue differentiation of the tumor(P>0.05).110 cases out of 112 patients were evaluable for efficacy, including esophageal 3 PR,6 SD,12 PD cases respectively and the disease control rate was 42.9%;gastric 1 CR,5 PR,10 SD,20 PD cases respectively and the disease control rate was 44.4%; colorectal cancer 2 CR,8 PR,13 SD,30 PD and the disease control rate was 43.4%.The tail length was utilized as an evaluation index of DRR, the results suggesting the DRR of esophageal(r=-0.500,p=0.021),gastric cancer(r=-0.546, p=0.001),colorectal cancer(r=-0.362, p=0.008) were negatively correlated with chemotherapy. Using tail-phase as an evaluation index for DRR indicating esophageal(r=-0.481, p=0.027) and gastric cancer(r=-0.361, p=0.030) were negatively correlated with chemotherapy, no correlation with chemotherapy was shown in colorectal cancer(r=-0.256, p=0.064).Conclusion1、Compared with healthy subjects, the DNA repair capacity of esophageal cancer patients is low. Also patients with high DNA repair capacity only received worse curative effect of combined platinum chemotherapy. DNA repair rate can be used to predict the therapeutic effect of patients with advanced esophageal cancer on platinum based chemotherapy.2、Compared with healthy subjects, the DNA repair capacity of gastric cancer patients is low. Also patients with high DNA repair capacity only received worse curative effect of combined platinum chemotherapy. DNA repair rate can be used to predict the therapeutic effect of patients with advanced gastric cancer on platinum based chemotherapy.3、Compared with healthy subjects, the DNA repair capacity of colorectal cancer patients is low. Also patients with high DNA repair capacity only received worse curative effect of combined platinum chemotherapy. DNA repair rate can be used to predict the therapeutic effect of patients with advanced colorectal cancer on platinum based chemotherapy.