| Objective: E-cadherin (CDH1), as one of the cadherin members, relates with invasion and metastasis of various cancers. Polymorphisms in the promoter and untranslated region of E-cadherin gene have been associated with tumor deveploment and progression, via modifying its transcriptional activity and protein expression level. The aim of the study was to investigate the possible association of single nucleotide polymorphisms (SNP) CDH1-160C/A and -347G/GA of CDH1 gene in the promoter region, to cervical cancer in North China population.Methods: This hospital-based case-control study included 243 cervical cancer patients and 323 healthy controls. Genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. Polymorphisms of CDH1 gene were analyzed by PCR-restriction fragment length polymorphism analysis (RFLP).Statistical analysis was performed using SPSS11.5 software package. 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.Results:1 The distributions of CDH1 gene -160C/A, -347G/GA SNPs genotypes among healthy controls were compatible with those expected genotype frequencies from Hardy-Weinberg equilibrium (P=0.80, P=0.38).2 The frequencies of three genotypes (G/G, G/GA and GA/GA) of CDH1 gene -347G/GA SNP in cervical cancer patients and healthy controls were 46.5%, 38.7%, 14.8% and 54.2%, 39.3%, 6.5%, respectively. There was significant difference between the two groups (P=0.004). The frequencies of two alleles (G and GA) of CDH1 gene -347G/GA SNP in cervical cancer patients and healthy controls were 65.8%, 34.2% and 73.8%, 26.2%, respectively. The frequencies of the GA allele of the CDH1 gene -347G/GA SNP were significantly higher in cervical cancer patients (34.2%) than those in healthy controls (24.6%). There was statistical difference between the two groups (P=0.004). Compared with the G allele, the GA allele significantly increased the risk of cervical cancer (OR=2.66, 95%CI=1.46~4.78). Compared with the G/G genotypes, carries GA allele (G/GA+GA/GA) genotype has a trendency to increase the risk of cervical cancer (OR=1.36, 95%CI=0.97~1.89). When stratified by clinical type, carries GA allele (G/GA+GA/GA)genotype were significantly associated with the hollow type (OR=2.53, 95%CI=1.00~6.38). Furthermore, carries GA allele (G/GA+GA/GA) genotype were moderately increased risk or tumor size≥6cm of cervical cancer, with odds ratio at 1.74 (95%CI=0.96~3.16). There is no significant difference according to curative effect.3 The genotype and allele distributions of CDH1 gene -160C/A SNP were not significantly different in the cervical cancer group to the control group (P=0.31 and P=0.15). Compared to the C/A+A/A genotype, C/C did not significantly modify the risk of cervical cancer with odds ratio of 1.25 (95%CI=0.89~1.76). Stratification analysis showed that C/A+A/A genotype were tended to increase risk of the earlier stage cervical cancer (OR=1.45, 95%CI=0.98~1.95). Stratification analysis showed no significant difference between the patient and control groups in allele or genotype distributions of CDH1 gene -160C/A SNP according to the clinical stage, tumor size and curative effect of cervical cancer (P>0.05).4 The combined effect of CDH1 gene -160C/A and -347G/GA SNPs was analyzed by EH and 2LD software. The result showed that the -160C/-347G haplotype was the most common, which was 59.7%, four haplotypes (-160C/-347G, -160C/-347GA, -160A/-347G and -160A/-347GA) of CDH1 gene -160C/A and -347G/GA SNPs were significantly different between the patient and control groups (P=0.01). In addition, linkage disequilibrium analysis showed that the CDH1 gene -160C and -347G polymorphisms were in a linkage diseqilibrium (D'=0.79, SD=0.07).5 The frequencies of three genotypes (G/G,G/GA and GA/GA) of CDH1 gene -347G/GA SNP in HPV-16, 18 infection (+) and (-) group were 44.7%, 39.2%, 16.1% and 61.5%, 34.6%, 3.8%, respectively. There was no significant difference between the two groups (P=0.096). Compared with the G/G genotypes, carries GA allele ( G/GA+GA/GA )genotype did not significantly modify the HPV-16, 18 type infection (OR=1.98, 95%CI=0.86～4.56).6 The genotype distributions of CDH1 gene -160C/A SNP were not significantly different in the HPV-16, 18 infection(+) and (-)group (P=0.72). Compared to the C/A+A/A genotype, C/C did not significantly modify the HPV-16, 18 type infection with odds ratio of 0.81 (95%CI=0.39～1.84).Conclusions:1 The CDH1 gene -160C/A SNP may have no susceptibility to the cervical cancer.2 CDH1 gene -347GA/GA genotype carriers were significantly increased the risk of cervical cancer.3 CDH1 gene -160C/A ,-347GA/GA SNPs genotype carriers were no significantly to the HPV-16, 18 infection.ss4 Although the CDH1 gene -160C/A and -347G/GA SNPs showed linkage disequilibrium. The -160A/-347GA haplotype significantly increased the risk of cervical cancer, compared with -160C/-347GA haplotype.
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