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Association of Single Nucleotide Polymorphisms in the nm23 Genes with Epithelial Ovarian Carcinoma

Author: QinJingJing
Tutor: KangShan；LiZuo
School: Hebei Medical University
Course: Obstetrics and Gynaecology
Keywords: nm23 single nucleotide polymorphism epithelial ovarian cancer susceptibility haplotype
CLC: R737.31
Type: Master's thesis
Year: 2011
Downloads: 7
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Abstract


Objective: Ovarian cancer is the leading cause of cancer death from gynecologic malignancies, with an annual incidence of over 200,000 in the worldwide. Epithelial ovarian carcinomas (EOC) account for nearly 90% of all ovarian malignancies. Despite significant advances have been made in diagnosis and treatment in the last decades, the prognosis of ovarian cancer remains poor, with an approximately 25%-30% overall 5-year survival rate. Though the etiopathogenisis of ovarian cancer is not very clear now, some studies have found that the development of ovarian cancer and genetic susceptibility are closely linkde. Therefor, it is the effective way to improve the survival rate of ovarian cancer to look for predisposing genes, high-risk group and early diagnosis method.nm23 is an important gene for the suppression of cancer metastasis, which is closely related to metastatic progression in many types of human cancer including ovarian cancer. Several studies have shown that the polymorphisms (rs16949649T/C and rs2302254C/T) within nm23 promoter might be associated with the risk of many cancers. In this paper, we studied the association between polymorphisms (rs16949649 T/C and rs2302254C/T) of nm23 and the risk of epithelial ovarian cancer. By this way, we hope to offer some evidences for the prevention and therapy of ovarian cancer at molecular level.Methods: This population-based case-control study included 302 ovarian cancer patients and 302 healthy controls. 5 ml of venous blood from each subject was drawn in vacutainer tubes. Genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. nm23 rs16949649T/C and rs2302254C/T SNPs were genotyped by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis. Statistical analysis was performed using SPSS13.0 software package (SPSS Company, Chicago, Illinois, USA). Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. The t test was used to examine the difference of ages between cases and controls. Univariate comparisons of allele and genotype distribution were performed using Chi-square test. The odds ratio (OR) and 95% confidence interval (CI) were calculated using an unconditional logistic regression model. The nm23 rs16949649T/C and rs2302254C/T haplotype frequencies and linkage disequilibrium coefficient were estimated by using EH linkage software and 2ld software. P<0.05 was considered significant for all statistical analyses.Results:1 The distributions of nm23 rs16949649T/C and rs2302254C/T genotypes among healthy controls were compatible with those expected from Hardy-Weinberg equilibrium (P>0.05).2 The genotype and allele distributions of nm23 rs16949649T/C were not significantly different between cases and controls (P=1.00 and P=0.22). Compared to C/T+C/C genotype, T/T genotype did not significantly modify the risk of ovarian cancer with odds ratio of 1.18 (95%CI=0.84-1.64).3 The genotype and allele distributions of nm23 rs2302254C/T were not significantly different between cases and controls (P=0.15 and P=0.38). Compared to C/T+T/T genotype, C/C genotype did not significantly modify the risk of ovarian cancer with odds ratio of 1.11 (95%CI=0.81-1.54).4 Stratification analysis showed no significant difference between the cases and control groups in allele or genotype distributions of nm23 rs16949649T/C and rs2302254C/T according to the pathological type, clinical stage and patient age of epithelial ovarian cancer (P>0.05).5 The results of the 2LD program analysis showed that the nm23 rs16949649T/C and rs2302254C/T polymorphisms displayed linkage disequilibrium (D′=0.92) in healthy subjects. Haplotype analysis showed that Trs16949649-Crs2302254 was the commonest haplotype in healthy controls (44.6%), followed by the Crs16949649-Crs2302254 (31.5%), Trs16949649-Trs2302254 (14.0%) and Crs16949649-Trs2302254 (9.9%) haplotypes. However, there was no significant difference between EOC patients and controls in the overall distribution of the nm23 haplotypes (P>0.05).Conclusions:1 The nm23 rs16949649T/C SNP may have no susceptibility to the epithelial ovarian cancer in the Northern Chinese women.2 The nm23 rs2302254C/T SNP may have no susceptibility to the epithelial ovarian cancer in the Northern Chinese women.3 nm23 rs16949649C/T and rs2302254C/T polymorphisms displayed linkage disequilibrium, however, the four haplotypes were not association with the risk of epithelial ovarian cancer developing.

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