The Relationship Between Polymorphisms In XPG C46T Gene And Prognosis In Colorectal Carcinoma

Objective: Colorectal cancer including rectum cancer and colon cancer is thefamiliar malignant tumor, recent years the incidence of colorectal cancer has beenincreasing quickly, it is the important research direction for the treatment of end-stagerectum cancer to improve surgical excision rate, to reduce the reccurence, and toprolong the life. as the comprehensive application of the new medicine, such asoxaliplatin, the short-term effective rate and life cycle of end-stage rectum cancer havebeen improved greatly. But to the individual of patient getting tumor, there is obviousindividual difference to sensitivity of the platinum class medicine. The DNA repairgene can play an important role in the drug resistance to oxaliplatin chemotherapy to thepatients. Nucleotide excision repair pathway is one of the main pathways for DNArepair, has close relationship with resistence of platinum class medicine. Singlenucleotide polymorphism of nucleotide-excision repair pathway and relevance ofplatinum class medicine have less research, and have inconsistent conclusion among allkinds of research, therefore, there is the important clinical significance to check outpredictive index which can predict effect to treat colon cancer patient with the platinumclass medicine.ERCC5is also called XPG, which is one of keytypes of NER repairpathway, but at present there are few reports to XPD gene polymorphism withchemotherapy sensitivity and prognosis. According to the above research result, throughthis experiment to study the relationship between DNA repair gene and FOLFOX4chemotherapy in the end-stage colorectal cancer patients, futher research therelationship between treatment effect after chemotherapy and TTP in XPG differentgenetype patient.Method: Collected71patients who are treated at our hospital from September2009to2010.Patients were required to have pathologically confirmed IIIB or IV end-stage colorectal cancer.ALL the patients in the group were take FOLFOXchemotherapy treatment which has oxaliplatin as foundation, it is: Before thechemotherapy, extracts peripheral blood2ml, after citric acid sodium antifreeze,withdraws plasma DNA samples and purifies it, and then design the goal genefragment’s upstream and downstream directly,by polymerase chain-restrictivefragment length polymorphism (PCR-RFLP) the method examines XPG the C46T thepolymorphism of gene, then analyzes the relationship between the chemotherapysensitivity and different gene type.Result:1） Among the71end-rage colorectal cancer patients, there were43XPGC/C examples,23XPG C/T examples and5T/T example, the total effectiveness:60.56%,32.39%and0.07%;2）After four-week oxaliplatin with5-Fluorouracil,Calcium Folinate biochemical modulation treatment, CR was0, PR+RD was43, PDwas28. The total number of patients who showed sensitivity to oxaliplatin was43, thetotal effectiveness was60.56%. In43profitable patients, there were31patients with thewild type gene XPG C46C, clinical profit rate was72.09%; there were10patients withthe mutagenicity allele gene XPG C46T, clinical profit rate was43.48%; there were2patients with the double mutagenicity allele gene XPG T46T, clinical profit rate was40%. There was significant difference among the three groups, p<0.05. Gender, age, thesite of the tumor and different organ site have no relationship with efficacy, p>0.05.There was no statistical significance. XPG C46T different type gene had correlationwith chemotherapeutic efficacy,p<0.05, the differences had a statistical significance;3）The71end-rage colorectal cancer patients were treated with oxaliplatin with5-Fluorouracil, Calcium Folinate biochemical modulation, and in the process of thetreatment, they showed myelosuppression as the main side effect, and leukocytedecrease was I°—II°, gastrointestinal reactions were nausea, vomit and diarrhea withthe I°liver injury and peripheral neuritis. There was no differences among the sideeffects in the above chemotherapy process. P>0.05;4） After the four-week FOLFOX4treatment with oxaliplatin, the MTTP of them was226days(7.5months), the MTTPwas297days(9.9months) for patients with XPG C/C genotypes, the MTTP was178days (5.9months) for patients with XPG C/T and XPG T/T genotypes. There was muchstatistical significance in the differences between C/C compared with C/T and T/T.x2=17.737，P<0.01;5. Gender, age, the site of the tumor and different organ site have norelationship with MTTP,p>0.05. There was no statistical significance. XPG C46Tdifferent type gene had correlation with MTTP of the71end-rage colorectal cancer patients, OR+2.245,95%CI:1.645-5.27, P<0.05.the differences had a statisticalsignificance.Conclusin:1） Among the71end-rage colorectal cancer patients, there were43XPG C/C examples,23XPG C/T examples and5T/T example, the total effectiveness:60.56%,32.39%and0.07%;2） After four-week oxaliplatin with5-Fluorouracil,Calcium Folinate biochemical modulation treatment, CR was0, PR+RD was43, PDwas28. The total number of patients who showed sensitivity to oxaliplatin was43, thetotal effectiveness was60.56%. In43profitable patients, there were31patients with thewild type gene XPG C46C, clinical profit rate was72.09%; there were10patients withthe mutagenicity allele gene XPG C46T, clinical profit rate was43.48%; there were2patients with the double mutagenicity allele gene XPG T46T, clinical profit rate was40%. There was significant difference among the three groups, p<0.05. Gender, age, thesite of the tumor and different organ site have no relationship with efficacy, p>0.05.There was no statistical significance.XPG C46T different type gene had correlation withchemotherapeutic efficacy,p<0.05, the differences had a statistical significance;3）The71end-rage colorectal cancer patients were treated with oxaliplatin with5-Fluorouracil,Calcium Folinate biochemical modulation, and in the process of the treatment, theyshowed myelosuppression as the main side effect, and leukocyte decrease was I°—II°, gastrointestinal reactions were nausea, vomit and diarrhea with the I°liver injuryand peripheral neuritis. There was no differences among the side effects in the abovechemotherapy process. P>0.05;4） After the four-week FOLFOX4treatment withoxaliplatin, the MTTP of them was226days(7.5months), the MTTP was297days(9.9months) for patients with XPG C/C genotypes, the MTTP was178days (5.9months)for patients with XPG C/T and XPG T/T genotypes. There was much statisticalsignificance in the differences between C/C compared with C/T and T/T. x2=17.737，P<0.01;5） Gender, age, the site of the tumor and different organ site have norelationship with MTTP, p>0.05. There was no statistical significance. XPG C46Tdifferent type gene had correlation with MTTP of the71end-rage colorectal cancerpatients, OR+2.245,95%CI:1.645-5.27, P<0.05.the differences had a statisticalsignificance.