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The Association Of The MDM2 Gene Polymorphism With The Risk Of Colorectal Cancer

Posted on:2017-09-05Degree:MasterType:Thesis
Country:ChinaCandidate:S P WangFull Text:PDF
GTID:2334330485473905Subject:Surgery
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Objective:To explore the relationship between MDM2(murine double minute)gene rs2279744 and rs117039649 SNPs and genetic susceptibility to colorectal cancer,want to providing a new theoretical basis for the early diagnosis and treatment of colorectal cancer at the molecular and gene level.Methods:From February 2014 to February 2016,a total of 371 colorectal cancer patients who treated in the Fourth Hospital of Hebei Medical University and 199 healthy controls were enrolled in the case-control study.The leucocyte DNA were extracted with Proteinase K digestion-saturated sodium chloride salting out method.Two SNPs genotype frequency distribution of MDM2 gene,rs2279744 and rs117039649,were analyzed using polymerase chain reaction-ligase detection reaction(PCR-LDR)method.The experimental data SPSS13.0(SPSS Company,Chicago,Illionis,USA).The age differences in and control group were tested with t test;Respectively,gender differences,the frequency of allele frequency and genotype distribution of rectal cancer group and colon cancer group were analyzed with chi-square test.And genotype frequency distribution chain balance were analyzed by using the Hardy-Weinberg.Logistic regression is used to calculate the ratio of relative risk degree than(odds thewire,OR)and 95% confidence interval(the confidence interval,CI).Results:1 Application of the law of Hardy-weinberg to test the genotype frequencies of rs2279744 and rs117039649 in the control population,the results P> 0.05,indicated that the population is representative.2 The frequency of G and T of MDM2 rs2279744 in rectal cancer patients and the control group were 67.70%?32.30%? 59.29%?40.71%.There was significant difference between the two groups(P=0.01,P<0.05).The frequency of G and T of MDM2 rs2279744 in colon cancer patients and the control group were 67.90%?32.10%? 59.29%?40.71%.There was significant difference between the two groups(P=0.01,P<0.05).The genotype frequency of GG,GT,and TT in rectal cancer patients and control group were 53.59%?28.23%?18.18%? 35.18%?48.24%?16.58%.Compared with the GT genotype,the GG and TT genotypes increased the risk of rectal cancer,(OR=2.603,95%CI=1.68-4.05 and OR=1.847,95%CI=1.06-3.31).The genotype frequency of GG,GT,and TT in colon cancer patients and control group were 54.32%?27.16%?18.52%? 35.18%?48.24%?16.58%.it was significant(P<0.05).Compared with the GT genotype,the GG and TT genotypes increased the risk of colon cancer.(OR=2.743,95% CI=1.71-4.41 and OR=1.983,95%CI=1.08-3.56).3 The frequency of G and C of MDM2 rs117039649 in colon cancer patients and the control group were 98.77%?1.23% ? 98.74%?1.26%.There was no significant difference between the two groups(P=0.97,P>0.05).The frequency of G and C of MDM2 rs117039649 G/C in rectal cancer patients and the control group were 99.28%?0.72% ? 98.74%?1.26%.There was no significant difference between the two groups(P=0.43,P>0.05).The genotype frequency of GG and GC in rectal cancer patients and control group were 98.56%?1.44%? 97.98%?2.02%.There was no significant association between the GG and GC genotypes of rectal cancer patients and control group(OR=0.565,95%CI=0.13-2.39).The genotype frequency of GG and GC in colon cancer patients and control group were 97.53%?2.47% and 97.98%?2.02%,There was no significant association between the GG and GC genotypes of colon cancer patients and control group(OR=0.982,95% CI=0.26-3.72).4 In rectal cancer patients,there was linkage disequilibrium between rs2279744 and rs117039649(D'=0.492).The most frequent haplotype was rs2279744G-rs117039649G(59.04%),then was rs2279744T-rs117039649G(39.70%)?rs2279744T-rs117039649C(1.01%)and rs2279744G-rs117039649C(0.25%).The haplotype of rs2279744G-rs117039649 G could increase the risk of rectal cancer(OR=1.438,95%CI=1.08-1.92).The haplotype of rs2279744T-rs117039649 G could reduce the risk of rectal cancer(OR=0.709,95%CI=0.53-0.95).The haplotype of rs2279744G-rs117039649C?rs2279744T-rs117039649 C were unrelated to the disease.In colon cancer patients,there was linkage disequilibrium between rs2279744 G/T and rs117039649 G/C(D'=0.021).The haplotype of rs2279744G-rs117039649 G could increase the risk of colon cancer(OR=1.447,95%CI=1.07-1.97).The haplotype of rs2279744T-rs117039649 G could reduce the risk of colon cancer(OR=0.688,95%CI=0.51-0.94).The haplotype of rs2279744G-rs117039649 C and rs22797 44T-rs117039649 C were unrelated to the disease.Conclusions:1 The gene polymorphism of MDM2 rs2279744 may be associated to colorectal cancer.Compared with the GT genotype,the GG and TT genotypes increased the the risk of colorectal cancer.2 It may has no significant correlation between MDM2 gene rs117039649 and the colorectal cancer.3 In colorectal cancer patients,there was linkage disequilibrium between MDM2 rs2279744 and rs117039649.The haplotype of rs2279744G-rs117039 649 G could increase the risk of colorectal cancer.The haplotype of rs2279744T-rs117039649 G could reduce the risk of colorectal cancer.
Keywords/Search Tags:Colorectal Cancer(CRC), MDM2, rs2279744/rs117039649, Polymorphism, Susceptibility
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