Study On The Association Of NF-?B Inflammatory Signaling Pathways Genepolymorphisms, Environmental Factors And Oral Maxillofacial Benign Tumors

Objective To investigate the independent and combined effects of the environmental factors and gene polymorphisms in NF-?B inflammatory signaling pathways on oral maxillofacial benign tumors.Methods 1.A case-control study was conducted with 542 patients and 1133 control subjects.Patients were recruited from the First affiliated hospital of Fujian Medical University with pathologic confirmation.All healthy controls were enrolled from hospital visitors and community population,and were frequency-matched to the cases by age(±3 year)and gender.Eligible subjects were personally interviewed using a questionnaire.Univariate and multivariate unconditional logistic regression and crossover analysis were used to identify the influence factors for oral maxillofacial benign tumors,and then the gender differences and interactions of these factors were also be explored.2.3m L blood samples were collected from patients and controls for DNA extraction.The genotypes of NFKB1-94ins>del(rs28362491),NFKBIA 2758G>A(rs696)polymorphisms were determined by PCR-RELP.The genotypes of NFKB1-826C>T(rs2233406)polymorphisms were identified by Mass Array.Univariate and multivariate unconditional logistic regression,crossover analysis were used to evaluatethe independent and combined effects of the polymorphisms and environmental factors on the susceptibility of oral maxillofacial benign tumors.Results 1.The risk factors for oral maxillofacial benign tumors included: cigarette smoking index(<1000 and ?1 000),passive smoking(?18 years old),cooking oil fumes exposure,years of wearing denture(>10 years),recurrent oral ulceration.The protective factors fororal maxillofacial benign tumors included: tea consumption(moderate concentration),intake of eggs(?3 times per week),fruits(>1 times per week,?times per day),beans and soy products(?3 times per week).2.Female passive smoking,cooking oil fumes exposure,years of wearing denture(>10 years)were more closely associated with the risk oforal maxillofacial benign tumors than men.The particularly strong beneficial effects were observed in female intake of fruits and the frequency brush teeth(?2times per day)than men.3.There was an additive and multiplicative interaction between passive smoking and cooking oil fumes in women,while the additive and multiplicative interaction between smoking and drinking was also found in men.4.The genotype distribution of NFKB1 rs28362491 was different between cases and controls(P<0.05).In co-dominant genetic model,rs28362491 Del/Del genotype could increase the risk of oral maxillofacial benign tumors(OR:1.736,95%CI: 1.065-2.827);in recessive genetic model,Del/Del genotype was also associated with an increased risk oforal maxillofacial benign tumors(OR: 1.629,95%CI: 1.072-2.473);Although the frequency of T allele of NFKBIA rs2233406 was significantly higher in patients with oral maxillofacial benign tumors than controls,no associations between NFKBIA rs2233406,rs696 polymorphisms and the susceptibility of oral maxillofacial benign tumors were found.5.In the gene-environment interaction,smokers with rs28362491 Del/Del genotype showed significantly increased risk of oral maxillofacial benign tumors(OR: 3.685,95%CI: 1.814-7.488),and there was an multiplicative interaction between rs28362491 Del/Del genotype and smoking(ORmultiplicative: 2.984,95%CI: 1.503-5.924).Similarly,combination of Del/Del genotype and drinking also increase the risk of oral maxillofacial benign tumors(OR: 2.759,95%CI: 1.242-6.128),with an multiplicative interaction(ORmultiplicative: 2.202,95%CI: 1.008-4.811).Additionally,subjects with Ins/Ins+Ins/Del genotype and recurrent oral ulceration had a nearly 5-fold increased risk of oral maxillofacial benign tumors(OR: 4.975,95%CI: 1.359-18.208).Particularly decreased OR was found in those with Ins/Ins+Ins/Del genotype and intake of green leafy vegetables more than 1 times per day(OR: 0.527,95%CI: 0.342-0.812).Conclusions 1.Smoking and alcohol drinking are the major risk factors for male oral maxillofacial benign tumors;while passive smoking and cooking oil fumes exposure are the major risk factors for female oral maxillofacial benign tumors.Increasing intake of vegetables,fruits,beans and soy products,and maintaining good oral hygiene can reduce the risk of oral maxillofacial benign tumors.2.Women may be more affected by passive smoking and cooking oil fumes exposure than men.Fruits intake and brushing teeth(>1 times per day)may be have particularly strong beneficial effect on female oral maxillofacial benign tumors.3.NFKB1 rs28362491 gene polymorphism is associated with susceptibility to oral maxillofacial benign tumors,with an additive multiplicative interaction on smoking/drinking.