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The Relationship Between the K-ras Gene Mutations and the Efficacy of Cetuximab in Colorectal Cancer
Author: YangXiaoFei
Tutor: LiuJiWei
School: Dalian Medical University
Course: Oncology
Keywords: colorectal cancer K-ras gene gene mutation cetuximab
CLC: R734.3
Type: Master's thesis
Year: 2011
Downloads: 62
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Abstract
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Objective:Some studies have found that the curative effect is related with the state of the K-ras gene when the colorectal cancer patients accept the therapy of cetuximab. In this study, we analysed the mutation rate, mutational types of K-ras gene in colorectal cancer. We also studied the relationship between the K-ras gene mutations and the clinical pathologic characteristics, the curative effect of cetuximab and the prognosis.Methods:42 colorectal cancer patients who were confirmed from Oct. 2004 to Jun. 2010 were involved in this study. We extracted DNA from paraffin embedding tissues, and detected the sequence of the K-ras gene through PCR amplification. We analysed the mutation rate, mutational types of K-ras gene in colorectal cancer. The relationship between the K-ras gene mutations and the clinical pathologic characteristics was studied by statistical software. The curative effect in 20 patients who accepted the therapy of cetuximab was evaluated. We analyzed the relationship between K-ras gene mutations and the efficacy of cetuximab and prognosis.Results:Among 42 cases of colorectal cancer patients, there were 12 cases had tested the mutations of K-ras gene, 30 cases were wide type, and the mutation rate was 28.57%. Among the mutational cases, 10 cases were tested in codon 12 of exon 2, and the other 2 cases were tested in codon 13 of exon 2. The relationship between the K-ras gene mutations and the clinical pathologic characteristics was explored, and we found that there were no obvious variations (P>0.05) in different sex, age, primary position, infiltrating depth, differentiation degree, lymph node metastasis. The mutation rate was higher in lump type than that in ulcer type and infiltrating type; and it’s also higher with metastasis than that with no metastasis. Both of the differences were statistically significant (P<0.05).Among the 20 cases of colorectal cancer patients who accepted the treatment of cetuximab, the effective rate was higher in the patients with wide type K-ras gene than those patients with mutated K-ras gene type, and the difference was statistically significant (P<0.05). The disease control rate was higher in the patients with wide type K-ras gene than those patients with mutated K-ras gene type, and the difference was not statistically significant (P>0.05). The median PFS was 2.6 months in mutational type, and was 4.5 months in wide type. The difference was statistically significant (P<0.05). The median OS was 9 months in mutational type and 11 months in wide type. The difference was not statistically significant (P>0.05). The adverse reactions were mainly nausea, diarrhea, weary, acneform eruptions. And the reverse reactions in most patients were slight.Conclusions:1. The K-ras gene mutation rate of the colorectal cancer was 28.57%, and the codons 12 usually mutated from GGT to GTT or GAT.2. The K-ras gene mutation of the colorectal cancer was related with the whole figure and metastasis. The mutation rate was higher in lump type than in ulcer type and infiltrating type; and it’s also higher with metastasis than that with no metastasis. Both of the differences were statistically significant.3. The effective rate of the patients accepted the therapy of cetuximab was higher in wide type of the K-ras gene than which in mutational type, and the difference was statistically significant. The disease control rate was higher in wide type than which in mutational type, and the difference was not statistically significant.4. The median PFS of the colorectal cancer patients who accepted the therapy of cetuximab was longer in wide type of the K-ras gene than which in mutational type, and the difference was statistically significant. The median OS was not statistically significant in the difference between in the patients with wide type and mutational type K-ras gene.
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