The Epidemiological Study On The Association Of Single Nucleotide Polymorphisms In The JAK2/STAT3 Inflammatory Signaling Pathways And Environmental Factors With Oral Squamous Cell Carcinoma

[Objective]To study the independent and combined effects of the environmental factors on oral squamous cell carcinoma.To investigate the combined effects of the environmental factors and gene polymorphisms in the JAK2/STAT3 inflammatory signaling pathways to the development of oral squamous cell carcinoma.[Methods]1.A case-control study was conducted with 604 cases and 1343 controls in Fujian province.Patients were recruited from the First Affiliated Hospital of Fujian Medical University,which were newly diagnosed oral squamous cell carcinoma cases with pathologic confirmation.Control subjects were enrolled from hospital visitors and community population.Eligible subjects were personally interviewed using a questionnaire.Methods such as unconditional logistic regression model,random forest and crossover analysis were employed,to identify the environmental factors and combined effects of oral squamous cell carcinoma and estimate the adjusted odds ratios(ORs)and 95% confidence intervals(95%CIs).2.Desiging molecular epidemiology study,Genome DNA was extracted from each participates’ peripheral blood.SNPs on JAK2/STAT3 inflammatory signaling pathways were genotyped by MassARRAY platform.Unconditional logistic regression,random forest and crossover analysis were used to investigate the association of SNPs with oral squamous cell carcinoma and the interaction effects of SNPs and environmental factors.[Results]1.Multivariate unconditional logistic regression analysis indicated that passive smoke before the age of 18(OR=1.65,95%CI=1.27-2.15),wearing dentures(OR=1.43,95%CI=1.10-1.88),family history of cancer(OR=1.51,95%CI=1.11-2.05),cigarette smoking(OR=1.80,95%CI=1.28-2.52),alcohol drinking(OR=2.11,95%CI=1.59-2.81),recurrent oral ulceration(OR=5.70,95%CI=3.48-9.32)were risk factors of oral squamous cell carcinoma.Regularly taking supplements(OR=0.46,95%CI=0.30-0.70),regularly taking vitamin supplements(OR=0.62,95%CI=0.40-0.98),seafood no less than 3 times per week(OR=0.52,95%CI=0.38-0.70),green vegetables over once a day(OR=0.47,95%CI=0.37-0.59),fruits no less than 3 times per week(OR=0.51,95%CI=0.40-0.65),brushing tooth no less than 1 times per day(OR=0.54,95%CI=0.30-0.99)were the protective factors of oral squamous cell carcinoma.2.The STAT3 rs1053005 CT/CC genotype(OR=0.68,95%CI=0.48-0.97)and the STAT3 rs12949918 CT/CC genotype(OR=0.67,95%CI=0.46-0.97)significantly reduced the risk of oral squamous cell carcinoma,while the JAK2 rs2230724 AA genotype(OR=1.52,95%CI=1.03-2.23)obviously increased the risk of oral squamous cell carcinoma.3.The stratification analysis indicated that JAK2 rs2230724 GA genotype reduced the risk of oral squamous cell carcinoma in smokers and alcohol drinkers,while the AA genotype increased the risk of oral squamous cell carcinoma in smokers.STAT3rs1053005 CT/CC genotype reduced the risk of oral squamous cell carcinoma in female.4.The analysis of combined effects and interactions showed that,there were positive multiplication and addition interaction between cigarette smoking and alcohol drinking,cigarette smoking and fruits,there was positive addition interaction between cigarette smoking and brushing tooth.There was a negative multiplication interaction between rs1053005 and fruits.In addition,persons who carried rs1053005,rs12949918 and rs2230724 adverse genotype encountered significantly increased risk of oral squamous cell carcinoma.[Conclusions]1.passive smoke before the age of 18,wearing dentures,family history of cancer,cigarette smoking,alcohol drinking,recurrent oral ulceration were the major risk factors of oral squamous cell carcinoma.While regularly taking supplements,regularly taking vitamin supplements,seafood no less than 3 times per week,green vegetables over once a day,fruits no less than 3 times per week,brushing tooth no less than 1 times per day were identified as protective factors.2.The SNPs of rs1053005,rs12949918 and rs2230724 were related to susceptibility of oral squamous cell carcinoma.3.The combined effects and interactions between risk factors of oral squamous cell carcinoma can not be ignored.The carriers with adverse alleles should strengthen the prevention and control of oral squamous cell carcinoma early.