| Objective Esophageal Cancer(EC)is one of the human common gastroin- testinal malignancy. The incidence rate in the 8th, 6th cancer mortality rates in malignant. Ningxia autonomous region is one of the areas of high incidence of esophageal cancer. And the high incidence of esophageal cancer in the region consistent with multi-gene interaction between genetic susceptibility and environmental disease model. Although p21Waf1/Cip1 has a general rare mutation. The natural genetic variants of p21Waf1/Cip1 have thus emerged for study to enhance understanding of interindividual differences in cancer risk. This study was to investigate the correlation of three polymorphisms in the p21Waf1/Cip1 gene ,i.e., codon 31 in the coding region,IVS2+16 in intron 2 and one new single-nucleotide polymorphism (SNP) 309 in the promoter region of p21Waf1/Cip1to susceptibilities of esophageal cancer (EC).This subject may reveal the genetic mechanism of esophageal cancer and provide a reliable theoretical basis in Ningxia.Methods⑴Samples source : The 80 esophageal cancer (EC) cases were histopathologically confirmed to have esophageal squamous cell carcinoma between 2007 and 2009 in the Affiliated Hospital of Ningxia Medical University. The exclusion criteria included previous cancer and previous chemotherapy or radiotherapy,among of these there are 53 males and 27 females, the average age is 60±8.Two hundreds controls were randomly selected from a pool of healthy volunteers who visited the general health check-up center at the Affiliated Hospital during the same period,among of these there are 130 males and 70 females, the average age is 59±6. Demographic data were collected by brief interview. Blood samples from all subjects were collected intravenous anti-clotting 5ml. Resin-based DNA extraction kit extracted DNA, using PCR amplification of specific fragments were directly sequenced.⑵statistic:Descriptive statistical analysis and unconditional logistic regression were performed by using Statistical Analysis System software (version 8.01; SAS Institute, Cary, NC),using x 2test for categorical variables and t test for continuous variables. x 2tests were also used to evaluate differences in demographic variables: smoking, drinking, and p21Waf1/Cip1 genotype distributions in cases and controls. Hardy–Weinberg equilibrium was tested by comparing expected and observed genotype frequencies by x 2 tests. Logistic regression to calculate unconditional, gander, age, smoking, drinking multivariate adjusted relative risk level (odds ratio, OR) and 95% CI (confidence interval, CI), p <0.05 was used as the criterion for statistical significance.Result⑴The expression of codon31 Ser/Ser homozygote genotypes had significant difference from the esophageal cancer group and the control group(35.00 vs. 21.00%, p <0.05). The occurrence of the homozygous Ser/Ser genotype was associated with increased risk for development of esophageal cancer (OR = 2.542, 95%CI =1.3 47–4.730, p <0.05).⑵The genotype frequencies of IVS2+16 C/G were 55.00% (CC), 41.25% (CG), and 3.75% (GG) in the case group and 52.50% (CC), 42.00% (CG), and 5.50% (GG) in the control group.⑶Genotyping for SNP 309 4G/3G variation revealed genotype frequencies of 26.25% (4G/4G), 51.25% (4G/ 3G), and 22.50% (3G/3G) in the case group, and 31.50% (4G/4G), 48.00% (4G/3G), and 20.50% (3G/3G) in the control group. A multiple logistic regression model was used to estimate the association between the genotypes of IVS2+16 or SNP 309 and the risk of esophageal cancer. No obvious associations were observed.⑷The haplotype with the existing three SNP in p21WAF1/CIP1 gene were constructed by using PHASE software. The association analysis and logistic regression analysis showed that haplotype A (Arg-C-4G) and B (Ser-C-4G) had associations with cancer risk. The heterozygous form of haplotype A (HapA/-) was associated with decreased risk of esophageal cancer. However, homozygous haplotype B (Hap B/B) posed increased esophageal cancer risk (OR=5.784, 95%CI= 1.377– 24.300, p <0.05).⑸Compared with controls; there were more cigarette smokers and alcohol drinkers among cases (55 vs. 30%;36.25 vs. 14.5%). Both drinking and smoking increased the susceptibility for developing esophageal cancer (OR = 2.891, 95%CI=1.321-6.327, p <0.05;OR=2.577,95% CI=1.139–5.829, p <0.05).Conclusion⑴Ser homozygosity of p21 Waf1 / Cip1 conferred a risk for the process of developing esophageal cancer in Ningxia Han people.⑵IVS2 + 16 genotype and SNPS 309 genotype of p21 Waf1 / Cip1 were not alone influence in Ningxia area of esophageal cancer mortality risk.⑶HapA (Arg-C-4G) was associated with reduced risk of esophageal cancer.⑷In contrast, haplotype B (Ser-C-4G) homozygotes had increased probability of developing esophageal cancer, which was consistent with statistical study of individual SNPs.⑸Smoking, alcohol consumption in case ergometry exist between the significant difference. |
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