Effect Of GSTP1and XRCC1Polymorphisms On Survival Of Colorectal Cancer Among Patients Who Receiving Oxaliplatin-based Postoperative Adjuvant Chemotherapy

Object: To investigate the distribution characteristics of glutathione S-transferaseP1(GSTP1) and X-ray repair cross-complementing1(XRCC1) polymorphism incolorectal cancer (CRC) patients, to study the prognostic role of GSTP1and XRCC1polymorphisms in CRC patients treated with postoperative adjuvant chemotherapy, andthen to provide some genetic basis for therapeutic decisions for individualized therapy inCRC cases.Methods: A total of75cases of surgically resected colorectal cancers were consecutivelyselected from the First Affiliated Hospital of Soochow University between Jan.2010toMay.2012, all of which were followed-up until Jan.2014. All patients treated withoxaliplatin-based postoperative adjuvant chemotherapy. Genotyping of GSTP1Ile105Valand XRCC1Arg399Gln were conducted by serial procedures such as blood samples EDTAanticoagulant, genomic DNA extraction, polymerase chain reaction (PCR) amplification,gene sequencing and so forth. All the patients got accurate KPS system assessment(>60scores) and image examination(X-ray, CT scan, B ultrasound) as well as RT(regular bloodtest), whole biochemistry set, mainly hepatorenal function when every chemotherapy cyclestarted. The average interval between two chemotherapy cycles is about4weeks. Duringthe period,75patients received reviews of RT and hepatorenal functions set at outpatientevery2weeks. To analyze the relationship between the polymorphism of twogenes(GSTP1, XRCC1) and clinical outcomes after oxaliplatin-based postoperativeadjuvant chemotherapy.Results:(1) Of the75patients, the analysis of the polymorphism located at GSTP1A313G showed that52(69.3%) were homozygous for A/A genotype,20(26.7%) wereheterozygous for A/G genotype and3(4.0%) were homozygous for G/G genotype. The DNA sequencing analysis of the polymorphism located at XRCC1Arg399Gln showed that43(57.3%) were homozygous for G/G genotype,28(37.3%) were heterozygous for G/Agenotype, and4(5.4%) were homozygous for A/A genotype. Genotype frequencies forXRCC1and GSTP1polymorphisms were both found to be in Hardy-Weinbergequilibrium.(2) No significant associations were found between age, gender, differentiation,lymphonode status, TNM stage or chemotherapy regimens (P>0.05).(3) Reference to the incidence of chronic neural cumulative lesion, nausea and vomiting,diarrhea, oral mucositis or myelosuppression, XRCC1gene (GG) had lowerincidence(P<0.05). No significant associations were found between GSTP1genotype.(4) Univariate Analyses showed GSTP1gene (A/G+G/G) and XRCC1gene (G/A+A/A)were two factors for progression-free survival(PFS)(P<0.05). Cox multivariate analysisfound GSTP1gene (A/G+G/G) was an independent positive factor for PFS in colorectalcancer patients treated with postoperative adjuvant chemotherapy, while XRCC1gene(G/A+A/A) was an independent negative factor for PFS(P<0.05).Conclusion:(1) GSTP1I105V and XRCC1R399Q both have a certain proportion genemutation in this group and both conform to the Hardy Weinberg equilibrium rule.(2) GSTP1gene (A/G+G/G) and XRCC1gene (GG) genotype maybe associated with ahigher clinical response rate to oxaliplatin-based postoperative adjuvant chemotherapy.(3) GSTP1and XRCC1polymorphisms may likely to be a reliable marker of response tooxaliplatin therapy and help doctor plan more effective medication for individual CRCpatient.