Association Of ADPRT And XRCC1 Gene Polymorphisms With Susceptibility To Squamous Cell Carcinoma Of Cervix

Cervical cancer is the second most common cancer in women.High risk of human papillomavirus(HR-HPV) infection is the one of the important cause of cervical cancer.HPV oncogenes,E6 have been showed to be the main contributors to the development of cervical cancer probably due to the loss of p53 protein,intraction with XRCC1 protein,integration of host cell-cycle control,which leads to chromosome imbalances,DNA damage, cells immortalization and progressing malignancy.However,only a few HPV infection women developed cervical cancer.Studies showed the association of several risk factors which include active and passive smoking. Specific-carcinogens in cigarette induce DNA damage,enhance viral persistence,decrease host immunity system and cause cell malignancy. There are several DNA repair pathways maintain genetic integrity and repair damaged DNA.It has been identified that there are a number of single nucleotide polymorphisms(SNPs) in DNA repair genes.Those SNPs may result in subtle alternation in structure,function of the repair enzymes,ability of DNA repair system,even in susceptibility of the host to the development of carcinoma.X-ray repair cross-complementing group-1(XRCC1) interacts with DNA ligaseⅢand DNA polymeraseβin DNA base excision repair pathway as an important gene.Nowadays,three SNPS of XRCC1 had been found:C26304T (Arg194Trp),G27466A(Arg280His) and G28152A(Arg399Gln).The variant genotype of Arg399Gln results in change of XRCC1 protein,which had been showed in studies as a susceptive factor to lung cancer.Adenosine diphosphate ribosyl transferase(ADPRT),another important gene in BER,specifically binds to DNA strand breaks and poly (ADP-ribose) ate nuclear acceptor proteins(include itself) in BER.More studies focused on ADPRT Val762Ala polymorphism than other SNPs of ADPRT. XRCC1 Arg399Gln variantion is situated within the BRCT-1 region harboring the ADPRT binding domain.Studies indicated that gene-gene interaction of ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms increased risk of lung cancer.Objects:We performed a case-control study to investigate the association between SNPs of ADPRT T2446C and XRCCI G28152A and host susceptibility to squamous cell carcinoma of cervix in Hen people in China.Materials and methods:1.Colleting samples:72 peripheral blood samples were collected from cases with histological diagnosed SCC(squamous cell carcinoma) from Han people in China,whose ages ranged from 28 to 79.Patients with carcinoma from other organs or those have immediate family relationship with anyone in cases or controls were excluded.Meanwhile,176 peripheral blood samples of healthy people,that without personal or familial history of carcinoma and familial genetic disease,from Hen people in China were collected as controls.Ages ranged from 21 to 55.All controls had a histological or cytological diagnosed of normal or chronic cervicitis.2.Analyzing the genotypes:To amplify target fragments by PCR and to analyze the ADPRT T2446 and XRCC1 G28152A genotypes by DNA chip.3.Processing the data:A chi-square test was conducted to examine the presence of Hardy-Weinberg Equilibrium and the independence of genotype and allele frequencies between cases and controls.Odds ratios and 95%confidence intervals(95%CI) were adjusted for age,active smoking,passive smoking and HPV infection status and unconditional logistic regression model.Results:1.The genotypes frequencies of ADPRT T2446 and XRCC1G28152A in cases and controls were fit for Hardy-Weinberg Equilibrium.2.There were no statistical significance of ADPRT T2446C and XRCC1 G28152A allele frequencies in cases and controls.3.There were no statistical significance of ADPRT T2446C and XRCC1 G28152A genotype frequencies in cases and controls.4.Odds ratios of ADPRT T2446C,XRCC1 G28152A gene polymorphisms in different gentic models were no statistical significance.5.Odds ratios of ADPRT T2446C,XRCC1 G28152A gene polymorphisms in different gentic models were no statistical significance in HR-HPV infected population.6.Odds ratio of intraction in passive smoking and ADPRT T2446 polymorphism to SCC was no statistical significance.7.Odds ratio of intraction in passive smoking and XRCC1G28152A polymorphism to SCC was no statistical significance.8.Odds ratio of intraction in ADPRT T2446 and XRCC1G28152A polymorphism to SCC was no statistical significance.Conclusion:1.The allele frequencies of ADPRT T2446C and XRCCI G28152A maybe reflect the possible variation of common Han people in China.2.No interaction between ADPRT T2446C polymorphism and SCC,XRCC1 G28152A polymorphism and SCC in our study. 3.No interaction between passive smoking and ADPRT T2446C polymorphism,passive smoking and XRCCI G28152A polymorphism in SCC in our study.4.No interaction between ADPRT T2446 and XRCCI G28152A polymorphisms in SCC in our study.