| Backgrounds and ObjectiveCervical cancer is one of the most common malignant tumors of reproductive tract among women. Every year, about 20 million women die of cervical cancer all over the world. However, cervical cancer still is a leading cause of cancer death for Chinese women. In China, there are 131 500 new cases each year. Furthermore, the incidence of cervical cancer is going to increase and the patient is getting younger and younger.As a new genetic product which regulates the structure of heterobrachial chromosome, WAPL (wing-apart like) protein is firstly tested in Drosophila's body. hWAPL(human wing-apart like) protein, the product of WAPL's homologous gene in human's body, has been known as a cohesin binding protein, which makes cohesin protein separate from chromosome arm in time in the beginning of cell division through a direct interaction between regulating subunits of cohesin protein. The literature presents a strong relationship between the hWAPL gene and cervical cancer. Interestingly, the hWAPL gene in cervical cancer has been found to be high-expressed, and the expression level of the hWAPL gene and cervical lesions is positively correlated.Many of human's diseases are caused by a genetic mutation. Then single nucleotide polymorphisms(single nucleotide polymorphism, SNPs) are the variations in DNA sequence caused by the mutation of a single nucleotide polymorphism in the level of genome, which is most common form of the genetic variation in human's genome. The SNP site which can represent other SNPs'information is called tagSNP. It means a few of tagSNPs will be able to provide most of the patterns of genetic polymorphisms in the certain chromosome region. Therefore, tagSNPs can greatly improve the effectiveness of association analysis,hence achieving better statistical results by using less SNP sites.Although the research has revealed that there are positive correlations between WAPL gene and cervical cancer, there are no domestic or foreign reports referring to the associations between polymorphisms of the WAPL gene and the risk of cervical cancer. In order to approve our hypothesis that the WAPL gene is one of susceptibility genes of cervical cancer, in this study, we detected the tagSNP distribution of the hWAPL gene in Han women with cervical cancer by using MALDI-TOF technology. Current study will provide useful clues for etiologic research, prevention and treatment of cervical cancer.Materials and MethodsThe blood samples of 300 cases of hospitalized Han women were collected in 6 city and province hospitals of Henan Province from August 2008 to October 2009, including 150 cases and 150 controls.For case samples, all patients with cervical cancer had conventional pathological diagnosis and did not carried out pre-chemotherapy or pre-radiotherapy, including 132 cases of cervical squamous cell carcinoma,18 cases of cervical adenocarcinoma. Blood samples of the controls were taken from the women with normal cervix in the same period, including 129 cases of uterine fibroids,21 cases of pelvic organ prolapse.The average age was 48 years old from 23-67 in patients of cervical cancer and 53 years old from 27-78 in controls, respectively.Applying the centrifugal columnar rapidly extracting kit of genomic DNA, DNAs of 300 samples of whole blood with 0.4% EDTAK2 were extracted. SDS-AGE technology and GEL imaging system tested and controlled the quality of the extracted genomic DNA of whole blood.12 tagSNPs of the hWAPL gene were detected by using MALDI-TOF technology. The softwares of SPSS15.0 and Haploview4.2 were used to analyze the data of the gene types, alleles types and haplotypes of hWAPL gene, and initially screen tagSNPs sites of hWAPL genes related to cervical cancer.χ2 test analyzes the gene types and alleles types, and calculates OR value and 95% CI. All tests are two-sided tests,the level of a test is a=0.05.Results1 All the observations of alleles and genotypes of 12 SNPs tested in this study were in agreement with their expectations and in line with Hardy-Weinberg equilibrium law.2 The allele T of rs11595882, the allele C of rs10887621 C and the allele G of rs11202058 were significantly associated with increased risk of cervical cancer (χ2=11.36,P=0.001,OR=2.481,95%CI=0.954-2.029;χ2=4.235,P=0.040,OR=1.610, 95%CI=1.020-2.540;χ2=4.088,P=0.043,OR=1.479,95%CI=1.011-2.165, respectively).3 The genotypes of rs7083506(CC+CT), rs11595882(TT+TC), rs7918136(TT+TA) and rs11202058(GG+GA) were observed to be associated with an increased risk of cervical cancer(χ2=6.522, P=0.011,OR=3.273,95%CI=1.261-8.493;χ2=10.03, P=0.002,OR=2.510,95%CI=1.406-4.482;χ2=6.522,P=0.011,OR=3.273,95%CI= 1.261-8.493;χ2=6.522, P=0.011,OR=3.273,95%CI=1.261-8.493,respectively).4 By haplotype analysis, based on the distributions of 12 SNPs in Han women,10 haplotypes were generated. The haplotypes of H8 (CCCCACCTGTCG) and H10 (CCCCATCTGTCG) were associated with a significantly increased risk of cervical cancer(χ2=10.391,P=0.0013;χ2=6.055,P=0.0139, respectively).ConclusionThere are remarkable differences about the distributions of single nucleotide polymorphism sites of the WAPL gene (rs11595882 T, rs10887621 C and rs11202058 G) between the case group and the control group.The haplotypes of H8 (CCCCACCTGTCG) and H10 (CCCCATCTGTCG) increase the risk of cervical cancer. Our results suggest:(1)the polymorphisms of hWAPL gene might relate to cervical cancer of in Han women; (2) the hWAPL gene may be one of susceptibility genes of cervical cancer.Keywordscervical cancer hWAPL gene tagSNPs susceptibility gene...
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