| Research Background Colorectal cancer is one of the most common gastrointestinal malignancies in the world,but its causes and mechanisms have not been fully elucidated yet.In China,its morbidity and mortality are also increasing year by year.According to domestic and international guidelines for treatment of colorectal cancer,preoperative neoadjuvant chemoradiation for locally advanced rectal cancer can reduce the size of the tumor,increase the rate of cure and preservation of anus,reduce the rate of local recurrence and distant metastasis.However,not all rectal cancer patients undergoing preoperative neoadjuvant chemoradiation can benefit from it,and a small number of patients are less sensitive to neoadjuvant chemoradiation.Such patients may not only lose surgical opportunities,but also increase the patient’s psychological burden and economic burden.The radiation tolerance phenomenon of rectal cancer is the main reason that affects the rectal cancer patients’ neoadjuvant radiotherapy.Therefore,to screen predictors of chemoradiation sensitivity in patients with rectal cancer has become a difficult problem to be solved.Radiobiology studies have shown that DNA damage repair in cells after ionizing radiation is one of the major causes of poor radiotherapy.The main source of genetic variation in human DNA repair gene is a single nucleotide polymorphism(Single nucleotide polymorphisms,SNP),but there is evidence that,SNP and susceptibility susceptibility to colorectal cancer and treatment-related.Among them,XRCC1,ERCC1 and XPC are associated with DNA damage repair,so it may be related to the sensitivity of radiotherapy and chemotherapy in rectal cancer.Purpose This article aims to investigate the relationship between the single nucleotide polymorphisms(SNPs)of XPC,ERCC1 and XRCC1 in DNA repair genes and the sensitivity of neoadjuvant radiotherapy for rectal cancer.It can be used to predict the sensitivity of patients with rectal cancer to chemoradiotherapy and choose a reasonable treatment plan for patients with rectal cancer.Materials and Method Patients were collected from October 2016 to June 2018 in the Hospital,and were diagnosed as stage Ⅱ/Ⅲ(T3-4N0M0 or any T,N + M0)rectal cancer patients through colonoscopy and pathology.Patients receive 5ml venous blood before treatment with EDTA,and the tumor tissue was embedded in wax blocks.The patients underwent neoadjuvant chemoradiation and radiotherapy was treated with IMRT.On the same day,radiotherapy was given with capecitabine on the 1st to 14 th days and on the 22 nd to 35 th days.After the end of radiotherapy and chemotherapy,surgery was performed after 4-6 weeks of rest.The specific surgical method was decided by the surgeon.Next generation sequencing(NSG)was used to analyze the single nucleotide polymorphisms(SNPs)on the DNA repair pathway.Evaluation of the sensitivity of neoadjuvant chemoradiation was undergoing after surgery in patients.Clinicopathologic data and ERCC1,XPC and XRCC1 polymorphism were both analyzed through univariate analysis in order to find out significant associations with response to NCRT.Multiple logistic regression analysis was also operated to explore the independent influencing factors.By doing this,significant indicator of predicting the reponse to NCRT could be realized,which would be able to direct the individualized treatment of patients with LARC.SPSS16.0 software was used to statistically analyze the study data.Measured data were expressed as mean±SD(mean±SD).The difference between the two groups was analyzed by independent sample t test.The difference analysis of count data was performed using the chi-square test.Spearman correlation analysis was used for correlation analysis.P < 0.05 was considered statistically significant.Result Screening 55 patients with rectal cancer who meet the enrollment conditions.In the sensitive group,there were 20 males and 5 females with an average age of 55.8 years.In the control group,there were 19 males and 11 females with an average age of 54.7 years.There were 28 cases of TC/TT type with ERCC1 gene and 27 cases of TT type.There were 32 patients with GG type XRCC1 gene and 23 patients with GA/AA type.There were 33 cases of CC with XPC gene and 22 cases of AC/AA.Univariate analysis and analysis of clinical factors affecting different genotypes suggest that the polymorphism of ERCC1 gene was significantly associated with the sensitivity of neoadjuvant radiochemotherapy for rectal cancer(P<0.05).Patients with TC/TT were more sensitive to neoadjuvant chemoradiation than CC carriers.The differences of XRCC1 condone399 and XPC1 condone199 between the two groups were not statistically significant(P>0.05).The CEA level in the sensitive group was significantly lower than that in the control group,and the proportion of patients with CEA <5 ng/ml in the sensitive group(64.00%)was significantly higher than that in the control group(30.00%).The difference was statistically significant(P<0.05).Pretreatment CEA levels were significantly associated with the sensitivity of neoadjuvant chemoradiation(P<0.05).Pretreatment CEA levels below normal were sensitive to neoadjuvant chemoradiation.In Conclusion 1.The wild type of ERCC1 gene may be a specific marker for the sensitivity of neoadjuvant chemoradiation in rectal cancer.2.Pretreatment CEA levels were significantly associated with the sensitivity and efficacy of neoadjuvant chemoradiation. |
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