Association Of Three Single Nucleotide Polymorphisms Of The CDH1 Gene With Susceptibility To Epithelial Ovarian Carcinoma

Objective: E-cadherin (CDH1), as one of the cadherin members, relates with invasion and metastasis of various cancers also with development of tumor. Polymorphisms in the promoter and untranslated region of CDH1 gene have been associated with tumor development and progression, via modifying its transcriptional activity and protein expression level. This study was designed to investigate the association of single nucleotide polymorphisms on the CDH1 gene with the risk of epithelial ovarian carcinoma.Methods: This hospital-based case-control study included 207 cancer patients and 256 healthy controls, recording their case history, personal history and family medical history. Genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. CDH1 polymorphisms were analyzed by PCR-restriction fragment length polymorphism analysis (RFLP). Immunohistochemistry was used to measure the level of CDH1 in different genotypes of 3′UTR +54C/T.Statistical analysis was performed using SPSS11.5 software package (SPSS Company, Chicago, Illinois, USA). P<0.05 was considered significant for all statistical analyses. Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. Comparison of the CDH1 genotype, allelotype and haplotype distribution in cancer patients and healthy controls was performed by means of two-sided contingency tables using Chi-square test. The CDH1 haplotype frequencies and linkage disequilibrium coefficient were estimated by using EH linkage software and 2LD software. The odds ratio (OR) and 95% confidence Interval (CI) were calculated using an unconditional logistic regression model and adjusted by age and sex accordingly. Comparison of E-cadherin expression of different 3′UTR +54C/T genotype and different pathological category performed by means of rank test as well Comparison of E-cadherin expression of different 3′UTR+54C/T genotype was performed by means of two-sided contingency tables using Chi-square test.Results: The distribution of the CDH-1 -160 C/A, -347 G/GA, 3′-UTR C/T genotypes in the control group did not significantly deviate from that expected for a Hardy-Weinberg equilibrium. 1 There were no significant difference between patients and control women in genotype distribution of the CDH-1 -160 C/A (χ2=0.379, P=0.827). And there were also no significant difference in allelotype distribution of the CDH-1 -160 C/A between patients and control women (χ2=0.229, P=0.632). Compared with the C/C genotype, the carriers of'A' allele were not significantly modified the risk of developing endometriosis. The odds ratios were 1.076 (95%CI=0.729~1.588). 2 There were no significant difference between patients and control women in genotype distribution of the CDH-1 -347 G/GA (χ2=1.548, P=0.461). And there were also no significant difference in allelotype distribution of the CDH-1 -347G/GA between patients and control women (χ2=1.407, P=0.236). Compared with the G/G genotype, the carriers of'GA'allele were not significantly modified the risk of developing endometriosis. The odds ratios were 1.207 (95%CI=0.835~1.745). 3 There were significant difference between patients and control women in genotype distribution of the CDH-1 3′UTR+54C/T (χ2=10.854, P=0.004). And there were also significant difference in allelotype distribution of the CDH-1 3′UTR+54C/T between patients and control women(χ2=7.220, P=0.007). Compared with the T/T+C/T genotype, the carriers of'C'allele were not significantly modified the risk of developing endometriosis. The odds ratios were 1.846 (95%CI=1.267~2.690). 4 The results of the 2LD program analysis showed that CDH-1 -160C/A and -347G/GA polymorphism were link disequilibrium (D′=0.999582, SD=0.0040). There were significant difference distribution of the CDH1 haplotype difference between patients and control women (χ2=33.092, P=0.000). Compared with -160C/-347G haplotype, -160A/-347GA haplotype significantly increased susceptibility to epithelial ovarian carcinoma, with adjusted odds ratio of OR=48.607, 95%CI=2.912~806.221. But -160C/-347GA haplotype decreased susceptibility to epithelial ovarian carcinoma, with adjusted odds ratio of 0.661, 95%CI=0.455~0.961. -160A/-347G would not change onset risk of epithelial ovarian carcinoma, with adjusted odds ratio of 0.743, 95%CI=0.542~1.017. 5 In the tissue of patients with C/C genotype of CDH1 3′UTR+54C/T, the expression of CDH1 is significantly higher than that with the other genotypes (C/T+T/T) (χ2=2.182, P=0.029). 6 There were no significant difference between E-cadherin expression of different 3′UTR+54C/T genotype and different clinical stage (χ2=4.828, P=0.185). 7 There were no significant difference between E-cadherin expression of different 3′UTR+54C/T genotype and different pathological category(χ2=2.125, P=0.547).Conclusions:1 The CDH1 -160C/A and -347G/G polymorphism may not be associated with Susceptibility to epithelial ovarian carcinoma.2 The CDH1 -160C/A and -347G/GA SNP was imperfectly in linkage disequilibrium. The -160C allele tends to be linked to the -347G allele. The -160A/-347GA haplotype significantly increased the risk of developing epithelial ovarian carcinoma, compared with -160C/-347G haplotype.3 The CDH1 3′UTR +54C/T polymorphism may be associated with Susceptibility to epithelial ovarian carcinoma, and the C/C genotype of CDH1 3′UTR +54C/T might significantly influence onset risk of epithelial ovarian carcinoma. 4 There were significant difference between E-cadherin expression of the C/C genotype of CDH1 3′UTR +54C/T and the other genotypes (C/T+T/T).5 There were no significant difference between E-cadherin expression of different 3′UTR +54C/T genotype and different clinical stage and there were also no significant difference between E-cadherin expression of different 3′UTR+54C/T genotype and different pathological category.