The Study On The Association Between Selenium-enzymes Single Nucleotide Polymorphisms In GPx/TXNRD Gene With Oral Cancer

ObjectiveTo explore the effects of selenium on oral cancer;to explore the association between selenium-enzyme GPx/TXNRD gene polymorphism with oral cancer genetic susceptibility;cancer based on Cox and Fine&Gray models to explore the prognostic factor of oral cancer.Methods1.A total of 1245 oral cancer patients and 2715 controls were selected on our case-control study.Epidemiologic data were collected by personally interviewed using a questionnaire.Unconditional logistic regression model was used to analyze the relationship between the environmental factors and oral cancer.Further,the serum selenium was measured by ICP-MS on the collected of blood sample.Using the restrictive cubic spline to analyze the dose-response relationship between selenium level and risk of oral cancer.Using unconditional logistic regression model to analyze the relationship between the selenium and oral cancer,and we constructed three multivariate models,using the DCA curve to evaluate the best multivariate model.2.Molecular epidemiological study was designed and used in this study.We extracted DNA from the blood samples,and analyzed 11 SNPs of the selenium-enzyme GPx and TXNRD by using MassARRAY platform.Unconditional logistic regression analysis was used to analyze the association between SNPs with genetic susceptibility to oral cancer,and invesgate the interaction effects between genes and the environment factors.3.Prospective study were used to collect clinical data and follow-up data from 427patients with oral cancer.The Cox proportional hazard model and the Fine&Gray model were used to select the prognostic factors of selenium-enzyme SNPs and environmental for oral cancerResults1.The restricted cubic spline showed a significant negative correlation between selenium and the risk of oral cancer.Multivariate logistic regression analysis indicated that the beginning age of smoking<20 years old,passive smoking,daily alcohol drinking（20⁵0ml and>50ml）and taking pickled food≥1 times/week were risk factors of oral cancer,OR and 95%CI were 2.29（1.22⁴.29）,1.93（1.37².70）,2.36（1.33⁴.18）,2.66（1.42⁴.98）and 1.50（1.01².22）.Taking pickled food≥1 time/week,eggs≥3times/week,green vegetables≥1 time/day,fruit≥3 times/week and selenium levels≥170.86μg/L were protection factors of oral cancer OR and 95%CI were0.63（0.44⁰.90）,0.62（0.44⁰.86）,0.15（0.07⁰.31）,0.28（0.20⁰.40）and0.13（0.09⁰.20）.The DCA curve results showed that the multivariate model had a high clinical predictive effect when selenium and demographic factors were included.2.Unconditional logistic regression analysis indicated that the risk of oral cancer on GPx4 gene rs3746165 AG/AA genotype was 1.48 times higher than that of GG genotype,and its 95%CI was 1.05².09.The risk of oral cancer on TXNRD1 gene rs17202060 in CC genotype was 0.64 times that of TT/TC genotype,and its 95%CI was 0.42 to 0.98.The results of stratified forests showed that rs3746165 AG/AA genotype increased the risk of oral cancer in women compared to GG genotype.The combined effect showed that the rs3746165 AG/AA genotype and rs17202060 TT/TC genotype may increase the risk of oral cancer.3.Multivariate Cox proportional hazard model results showed that the degree of moderate differentiation,T₄,N_2-3-3 and recurrence were risk factors for death in oral cancer patients,and surgical treatment was a protective factor for oral cancer,and selenium-enzyme SNPs were not significantly associated with death in oral cancer.The multivariate Fine&Gray model showed that the moderate and poor degree of differentiation,N₁,N_2-3-3 and chemotherapy were risk factors for recurrence and metastasis in oral cancer patients,and selenium-enzyme SNPs were not significantly associated with recurrence and metastasis in oral cancer.Conclusions1.Selenium is an important factor for oral cancer.The multivariate model constructed by selenium level has a good clinical predictive effect.2.The beginning age of smoking<20 years old,passive smoking,daily alcohol consumption（20⁵0ml and>50ml）and taking pickled food are risk factors for oral cancer,while taking pickled food,eggs,green vegetables,fruit and selenium levels are protective factors for oral cancer.3.GPx4 gene rs3746165 and TXNRD1 gene rs17202060 are associated with genetic susceptibility of oral cancer risk.4.The degree of moderate differentiation,T₄,N_2-3-3 and recurrence are risk factors for death in oral cancer patients,surgical treatment is a protective factor for oral cancer.The moderate and poor degree of differentiation,N₁,N_2-3-3 and chemotherapy were risk factors for recurrence and metastasis in oral cancer patients.5.There is no significant correlation between selenium levels and prognosis of oral cancer.