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Association of p73 and MDM2 Polymorphisms with the Risk of Epithelial Ovarian Cancer

Author: WangDongJie
Tutor: KangShan；LiZuo
School: Hebei Medical University
Course: Obstetrics and Gynaecology
Keywords: p73 MDM2 Single nucleotide polymorphisms Epithelial ovarian cancer Genetic predisposition
CLC: R737.31
Type: Master's thesis
Year: 2010
Downloads: 24
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Abstract


Objective: Ovarian cancer is the most common cause of death in gynecological malignancies, of which 90% of epithelial ovarian cancer. Epithelial ovarian cancer incidence of occult, the rapid progress of advanced stage, about 70% of patients found the 5-year survival rate of only 25% to 30%. Studies have shown that genetic predisposition may play an important role in the occurrence of ovarian cancer. Therefore, the search for susceptibility genes to establish a high-risk groups, early diagnosis is an effective way to improve ovarian cancer survival. In recent years, p73 and MDM2 (murine a double minute 2) as a candidate tumor gene has become a focus for researchers. p73 is a candidate tumor suppressor gene, plays an important role in the regulation of cell cycle and maintaining cell stability, non-coding region of the second exon two single nucleotide polymorphisms (single nucleotide polymorphisms, SNPs) (G4C14/A4T14), stem-loop structure can be formed and influence gene expression. MDM2 is a proto-oncogene, is an important negative regulator of p73, thereby weakening its function through the inhibition of p73 transcriptional activity. In view of the p73, MDM2 in cell cycle control and apoptosis in the interaction, the present study was to investigate the p73 and MDM2 gene single nucleotide polymorphisms (SNPs) and epithelial ovarian cancer risk, from the molecular level for ovarian provide experimental evidence for the prevention, diagnosis and treatment of cancer. Methods: A hospital-based case - control study, 257 patients with epithelial ovarian cancer patients and 257 healthy volunteers were women (control group), collected all the research object peripheral venous blood 5 ml, to the sodium citrate anticoagulant proteinase K digestion - salting out method to extract leukocyte DNA. Polymerase chain reaction - restriction fragment length polymorphism (polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP) method of p73 G4C14/A4T14, MDM2 309T / G and MDM2 Del1518 / - the three SNPs sites genotyping. The data were analyzed using the SPSS 11.5 statistical software for processing. The genotype frequency distribution of the control group the χ2 test done Hardy-Weinberg equilibrium analysis. Age differences of the case group and control group using t test, genotype and allele frequency distribution χ2 test was used to compare non-conditional logistic regression to calculate the relative risk ratio (odds ratio, OR) and its 95% credible interval (confidence interval, CI). EH software analysis of MDM2 309T / G and MDM2Del1518 / - gene haplotype frequencies, 2ld software analysis of linkage disequilibrium. Using the likelihood ratio test (likelihood ratio test) to analyze the interaction between p73 and MDM2 gene. P lt; 0.05 for the difference was statistically significant. The result: a control group from the p73 G4C14/A4T14 and of MDM2 309T / G, Del1518 / - polymorphism genotype distributions were in Hardy-Weinberg balance (χ2 = 0.00, 1.00 and 0.64, all P values ??gt; 0.05). 2 ovarian cancer and control groups, p73 G4C14/A4T14 polymorphism genotype and allele frequency distribution of the difference was not statistically significant (P = 0.20 and P = 0.55). Compared with the GC / AT AT / AT genotype, GC / GC genotype and the risk of ovarian cancer, OR = 1.24 (95% CI = 0.87 to 1.77). Pathological type, clinical stage or diagnosed at age stratified analysis, the polymorphic p73 G4C14/A4T14 genotype frequency distribution of differences among the groups was not statistically significant (P greater than 0.05). 3 MDM2 309T / G genotype frequency (T / T, T / G, G / G) in ovarian cancer and control groups were 30.0%, 46.7%, 23.3% and 21.8%, 47.1%, 31.1 %, the difference was statistically significant (P = 0.046). Ovarian cancer group of MDM2 309T / G SNP G allele frequency (46.7%) was significantly lower than the control group (54.7%), the difference was statistically significant (P = 0.01). Compared with the T / T genotype, G allele type (T / GG / G genotype) can significantly reduce the incidence of epithelial ovarian cancer risk (OR = 0.65, 95% CI = 0.44 ~~ 0.97). Pathological type, clinical stage and age at the time of diagnosis stratified analysis found that G allele (T / GG / G genotype) can significantly reduce the endometrioid carcinoma, advanced ovarian cancer and ovarian cancer patients over the age of 50 cancer risk (OR = 0.53, 95% CI = from 0.31 ~~ 0.90; OR = 0.62, 95% CI = 0.40 ~~ 0.97; OR = 0.59, 95% CI = 0.38 ~~ 0.92). 4 of MDM2 Del1518 / - SNP genotype and allele frequency distribution in the case and control groups, the difference was not statistically significant (P = 0.68 and P = 0.45). Compared with the (/ -) (- / -) genotype / independent of the genotype and the risk of epithelial ovarian cancer (OR = 1.17, 95% CI = 0.83 ~ 1.65). Pathological type, clinical stage, and age of onset stratified analysis showed that carrying the MDM2 Del1518 / genotype increased mucinous ovarian cancer and the early onset of ovarian cancer risk trend (OR = 2.01, 95% CI = 0.93 4.37; OR = 1.64, 95% CI = 0.99 ~ 2.72), while no significant correlation with age of onset. 5 2ld software MDM2 309T / G and Del1518 / - two polymorphic sites combined analysis showed linkage disequilibrium phenomena (D '= 0.57, P = 0.00) between the two loci. The EH software MDM2 309T / G and Del1518 / - two points SNPs Haplotype analysis showed that the frequency of the four kinds haplotype (1518/T309, 1518/G309, -1518/T309 -1518/G309) of distribution in ovarian cancer and control groups showed no significant difference (P = 0.07), but compared with 1518/T309 haplotype, 1518/G309 -1518/G309 haplotype could significantly reduce epithelial ovarian The incidence of cancer risk (OR = 0.73, 95% CI = from 0.55 ~~ 0.98; OR = 0.65, 95% CI = 0.45 ~~ 0.96). 6 using the likelihood ratio test analysis of p73 G4C14/A4T14 SNP of MDM2 309T / G, Del1518 / - 2 SNPs between gene - gene interactions. The results showed that, between the p73 G4C14/A4T14 with MDM2 309T / G interaction (P = 0.03, OR = 0.89, 95% CI = 0.80 to 0.99); while the p73 G4C14/A4T14 with no obvious Del1518 / - interaction (P = 0.36). P73 G4C14/A4T14- (/ GG / G) carry (GC / AT AT / AT) compared with GC/GCp73 G4C14/A4T14-T/TMDM2 309T / G genotype of MDM2 309T / G genotype can significantly reduce ovarian incidence of epithelial cancer risk (OR = 0.55,95% CI = 0.31 ~ 0.98). Conclusion: 1 the p73 G4C14/A4T14 the gene polymorphism may be nothing to do with epithelial ovarian cancer genetic susceptibility. Carrying MDM2 309T / G polymorphism G allele type may significantly reduce the risk of epithelial ovarian cancer and type pathology with epithelial ovarian cancer, clinical stage and age at the time of diagnosis was significantly associated Therefore, 309G bits The gene may be the incidence of epithelial ovarian cancer a potential protective factors. 3 MDM2 Del1518 / genotype increase mucinous ovarian cancer and the early onset of ovarian cancer risk, while no significant correlation with age of onset. Existence of MDM2 309T / G and Del1518 / - two polymorphic sites the linkage disequilibrium, 1518/G309, and -1518/G309 haplotype could significantly reduce the risk of epithelial ovarian cancer. 5 p73 G4C14/A4T14 between MDM2 309T / G the obvious interaction in the p73 G4C14/A4T14 with no interaction Del1518 / -. (GC / AT AT / AT) p73 G4C14/A4T14- (T / GG / G) MDM2 309T / G genotype can significantly reduce the risk of epithelial ovarian cancer.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Female genital tumors > Ovarian tumors
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