Associations And Interactions Between EB Virus Infection And XRCC1 Arg399Gln Polymorphism In Nasopharyngeal Carcinoma

[Background]Nasopharyngeal carcinoma(Nasopharyngeal carcinoma, NPC) is a kind of cancer derived from nasopharyngeal mucosa epithelium and columnar epithelial. It has unbalanced geographical distribution and ethnic. EB virus(Epstein- Barr virus comes, EBV) infection is closely related to NPC, which eventually caused a variety of corresponding antibodies, including the VCA-IgA, EA-IgA and Rta-IgG. EBV plays an essential role in the occurrence and development of NPC and could escape immune surveillance through a variety of mechanisms.Other than EBV, some environmental factors and individual genetic susceptibility are also important factors with high risk in the pathogenesis of NPC. Of note, it is reported that abnormal function of some DNA repair gene, such as the X-ray repair cross complementary gene 1(XRCC1), is related to the occurrence and development of various cancers. The XRCC1 gene possesses three common single polymorphism nucleotides as C26304 T, G27466 A and G28152, with the corresponding amino acid residues of Arg194 Trp, Arg280 IIis and Arg399G1 n, respectively. This study aimed to investigate the interactions between EBV infection and XRCC1, and our work will help us to better understand the underlying mechanisms of susceptibility of NPC. [Objective]1. To investigate the clinical value of VCA-IgA, EA-IgA and Rta-IgG detection in diagnosing NPC, and find the optimum combination of VCA-IgA, EA-IgA and Rta-IgG in screening NPC.2. To assess the correlations between XRCC1 Arg399 Gln polymorphism and nasopharyngeal carcinoma risk.3. To trace the mutual interactions between XRCC1 polymorphisms and the risk of NPC. [Methods]1. The S/CO value of VCA-IgA, EA-IgA and Rta-IgG were evaluated from 2155 NPC primary patients and 6957 healthy cases in Fujian area using ELISA, and the positive as well as the constituent ratios were assessed.2. In the matched case-control study, 90 NPC patients and 75 healthy controls in Fujian area were enrolled. Genome DNA were extracted from the whole blood and then amplified via PCR. The PCR products were further purified and sent for DNA sequencing and eventually confirmed the genotype of XRCC1 Codon399. [Results]1. A total of 2155 NPC were included for the VCA-IgA, EA-IgA and Rta-IgG tests, among which, most of the cases were males with the middle age(41~60); the undifferentiated carcinoma of nasopharyngeal type(NCCN) possesses the occupies the main parts among all pathological types, whereas in different TNM stages, N2, M0 and III/IV accounted for the main parts, and the case size increased gradually with the increase of cases in T stage;2. In NPC group, the position rates of VCA-IgA, EA-IgA and Rta-IgG were 89.88%, 46.59% and 63.25%, respectively, yet the negative rates in healthy population were 89.65%, 96.89% and 94.87%, respectively, all with P values less than 0.01 in the two groups. The Youden index of these three EB antibodies were estimated to be 0.79, 0.43 and 0.58, respectively, whereas the area order under the ROC curve was VCA-IgA>EA-IgA>Rta-IgG;.3. VCA-IgA, EA-IgA and Rta-IgG positive yielded the highest risk(OR=167.64, 95%C.I.: 99.008-283.853), while VCA-IgA and Rta-IgG positive took the second place(OR=28.45, 95%C.I.: 22.069-36.675). Notably, the negative results of all three antibodies harbored the minimum risk(OR = 0.08, 95% C.I.: 0.065-0.090).4. VCA-IgA yielded the highest positive rate in NPC group(40~60 years, P<0.01), while Rta-IgG positive rate increased along with age, yet VCA-IgA accounts for the most part in NCCN pathological type. EA-IgA positive rate increased linearly relative to T stage, and VCA-IgA, EA-IgA and Rta-IgG positive rates increased linearly relative to N and clinical stage(P<0.01), but with no significant differencein M stage cases(P>0.05).5. VCA-IgA, EA-IgA and Rta-IgG positive is regarded as a high risk factor in NPC occurrence, especially that single VCA-IgA positive seemed to be achieve the highest OR value of 26.526(95%C.I.:11.190-62.884). Univairate logistic regression analysis showed that the OR value of patients with XRCC-1 Arg399GlnGG genotype was more higher that those AA genotype; XRCC-1 Arg399 Gln single nucleotide polymorphisms revealed remarkable correlations with EB virus infection in the occurrence of NPC(OR=20.755, 95%C.I.: 5.312-81.094). [Conclusions]1. The NPC occurred mainly in males with middle age, with the common type of NCCN, and most of them were diagnosed in III/IV stage, with the TNM stage of T2N2M0;2. The diagnostic value is estimated to be VCA-IgA>Rta-IgG>EA-IgA;3. The combination of VCA-IgA+/EA-IgA+/Rta+ was regarded as a high risk factor in NPC occurrence, whereas all negative results of these three tests was deemed as factor with low risk;4. VCA-IgA, EA-IgA and Rta-IgG positive rates were positively correlated with clinical stage, especially in N staging cases.5. Arg399GlnGG genotype is associated with the susceptibility of NPC; there were interactions between(XRCC1) Arg399 Gln single nucleotide polymorphisms and EB virus infection in NPC.