K-ras Gene Mutation Relationship With The Biological Behavior Of Colorectal Cancer Correlation Analysis And Adverse Reactions With FOLFOX

BackgroundIn China, colorectal cancer (colorectal cancer, CRC) located in the four incidenceof malignant tumors, is a common tumor. In recent years, the incidence of colorectalcancer increased gradually, with younger and younger, and is the second leadingcause of cancer-related death.Surgery is the most effective treatment of colorectal cancer, and chemotherapy andradiotherapy are the useful supplement of surgery. Only70percent of patientsdiagnosed of colorectal cancer can underwent radical resection, and about40percentof patients with stage Ⅱ,Ⅲ may have recurrence, so chemotherapy plays a veryimportant role for the these patients. In the past few years,5-FU is the main drug incolorectal cancer chemotherapy. In recent years, with the emergence of new drugssuch as irinotecan, oxaliplatin, at al, survival of advanced colorectal cancer patientshas improved significantly.Numerous experiments showed that the occurrence of colorectal cancer was relatedwith activation of multiple oncogenes or activation of tumor suppressor genes, forexample Ras oncogene. Ras oncogene family of K-ras, H-ras and N-ras threemembers, their majority of point mutation occurred in exon1’12thand13thcodon.K-ras gene status of three could be used to predict efficacy of anti-EGFR targetingdrug, and was an important indicator to select targeted treatment options of colorectalcancer patients.《2013(NCCN) Clinical Practice Guidelines in Colorectal Cancer》 noted that the patients before targeted therapy should be carried K-ras gene mutationdetection.The view that K-ras gene mutation could predict the effect and prognosis ofconventional chemotherapy was no consistent conclusion because of lackingpredictability indicators. This study revealed the molecular level changes of K-rasgene of colorectal cancer, revealed the biological behavior of the K-ras gene, revealedthe correlation relationship between K-ras gene mutation and adverse reaction ofFOLFOX chemotherapy, and explored the K-ras gene mutation can predict adverseeffects of conventional chemotherapy chemotherapy.ObjectiveThe study compared the advantages of quantitative PCR and direct sequencingdetection through quantitative PCR and direct sequencing detection of colorectalcancer K-ras gene mutation; The study explored the relationship between K-ras genemutation and colorectal cancer biology; Could K-ras gene mutation status predictadverse reactions of FOLFOX chemotherapy with colorectal cancer.MethodsThe study selected200patients with colorectal cancer and surgical treatment fromour hospital patients form December1,2011to October31,2012. ALL patients wereasked general, such as age, sex, name, and main clinical manifestations and others.Every one with surgery were carried pathological diagnosis and accepted FOLOFOXchemotherapy without anti-EGFR antibody therapy. Patients were assessed by KPSscores after the end of each cyde of chemotherapy. Their adverse reactions wereevaluated according to grading standards of common adverse reactions of anti-cancerdrugs recommended by WHO and were recorded. The study used quantitative PCRand direct sequencing detection to sequenced histopathology and differ thesequencing results of two methods. The study explored the relationship between K-rasgene mutation and colorectal cancer biology and the correlation between K-ras genemutation status and adverse reactions of FOLFOX chemotherapy. The study analyzed the relationship between K-ras gene mutation status and tumor size, degree ofdifferentiation, depth of invasion, TNM stage and CEA levels and explored thecorrelation between K-ras gene mutation status and adverse reactions of FOLFOXchemotherapy by using X2test of SPSS17.0statistical software.ResultsSeventy-three (73/200,36.5percent) of200patients with colorectal cancer carriedK-ras gene mutation, in which52cases carried mutation in12codon (52/200,26percent) and21cases carried mutation in13codon (21/200,10.5percent).K-ras gene mutation rate in different ages (<50years and>50years), and genderwas no significantly difference. K-ras gene mutation rate was no significantlydifference in different tumor size, location, degree of tumor cell differentiation anddepth of invasion (P>0.05), but was significantly difference in difference TNM stage(P＜0.05).118cases with colorectal cancer accepted1002cydes of FOLFOX chemotherapy.Adverse reactions of chemotherapy: I~II degrees of nausea and vomiting, abnormalsensory nerve, bone marrow suppression, diarrhea and liver dysfunction and othersymptoms, that were recovered in chemotherapy gap. All patients did not occur renaland cardiac toxicity, and did not delay or stop chemotherapy because of seriousadverse reactions. There was no correlation between K-ras gene mutation status andadverse reactions of FOLFOX chemotherapy.ConclusionsOur experiment showed that there were point mutations of K-ras gene in colorectalcancer and the mutation rate was36.5%; Codon12that the main location of themutation included the main types: the second G mutated to T or mutated to A.K-ras gene mutation rate was no significantly difference in different tumor size,location, degree of tumor cell differentiation and depth of invasion (P>0.05), but wassignificantly difference in difference TNM stage (P＜0.05). K-ras gene mutation canmake tumor certain invasive and has metastatic potential. Adverse reactions of FOLFOX chemotherapy of colorectal cancer were nosignificantly difference in different K-ras gene mutation status. K-ras gene mutationsstatus of colorectal cancer could not predict adverse reactions of chemotherapy.So, K-ras gene mutations as a molecular marker, was an important indicator todetermine the degree of malignancy of colorectal cancer and metastatic potential,but not to predict adverse reactions of chemotherapy.