Relationship Between XRCC1 Codon 399Gln Polymorphism And Irradiation Injured In Cervical Cancer

ObjectiveOur goal is to compare the clinical outcomes and toxicities of pelvic intensity-modulated radiation therapy(IMRT)and three-dimensional conformal radiation therapy(3D-CRT)as adjuvant postoperative treatment in patients with cervical cancer.In addition,we will also explore the relationship between XRCC1 condon 399 Gln polymorphism and radiotherapy-induced acute cystitis and proctitis in cervical cancer.Methods1.We collected 115 cervical cancer patients(confirmed by pathological biopsy)registered in the Cancer Center of Daping Hospital between April 2008 and December 2013.They were initially treated with radical hysterectomy and adjuvant pelvic external-beam radiation therapy(EBRT).Firstly we compared whether the baseline data of two types of radiation are non-significant.2.We compared the overall survival,disease-free survival,locoregional control and treatment-related complications between the two groups.3.We recruited 152 patients with cervical cancer(conformed by pathological biopsy).Single nucleotide polymorphisms(SNPs)in XRCC1 gene were analyzed by Sanger sequencing method.The relationship between these SNPs and the acute irradiation injury was evaluated.Results1.Patients were treated with pelvic radiothereapy after radical surgery.Two-year OS were 90.3% in the 3D-CRT group and 91.6% in the IMRT group(P = 0.674),and DFS were 88.8% and 86.0%,respectively(P = 0.722).There isn’t significant difference between them.The LRC was 93.2% in 3D-CRT group.Because locoregional failure occurred in only one patient in the IMRT group,we could not calculate a specific value for 2-year locoregional control.However,no significant difference in this parameter was observed between groups.2.The rates of acute gastrointestinal(GI)and genitourinary(GU)toxicity were lower in the IMRT group than that in the 3D-CRT group(GI,50% vs.84.3%,P = 0.009;GU,19.2% vs.56.2%,P = 0.007).3.In the 152 cases,the numbers of genotypes of XRCC1 Arg/Arg,Arg/Gln,Gln/Gln were 78,56,18,respectively.Among them,number of grade 2-3 acute cystitis is 47 cases;grade 2-3 acute proctitis had 100 cases.There are no grade 4 acute cystitis and proctitis.4.After adjustment for other clinical factors,multivariate Logistic regression analysis indicate that the XRCC1 399Arg/Gln and 399Gln/Gln were significantly associated with the development of grade 2-3 cystitis(OR 4.114;95% CI 1.746-9.693,OR=5.011;95% CI 2.169-11.575,respectively).In addition,it was also associated with higher incidence of grade 2-3 proctitis(OR=5.011;95% CI 2.169-11.575,OR=7.165;95% CI 1.506-34.092).Conclusion1.Our results indicate that IMRT can provide good clinical outcomes similar as those achieved with 3D-CRT.The OS,DFS and LRC had no significant statistical differences2.IMRT was associated with less acute gastrointestinal and genitourinary toxicity compared with 3D-CRT in patients who were adjuvanted pelvic radiotherapy after radical surgery.3.Our results showed that the SNPs of XRCC1 codon 399 were related with acute radiation cystitis and proctitis in cervical cancer.In addition,the XRCC1 399Arg/Gln and 399Gln/Gln were more likely to occur grade 2-3 cystitis and proctitis than wild type.4.We draw a conclusion that the SNPs of XRCC1 codon 399 have the potential of predictive value on radiotherapy side effects in cervical cancer.