The Association Study Of DNA Double-Strand Break Repair Gene NBS1 Polymorphisms With Susceptibility To Lung Cancer

[Objective]To study causes of lung cancer, the association of DNA double-strand break repair gene NBS1 polymorphisms with susceptibility to lung cancer, and the combined effects in etiology of lung cancer.[methods]A case-control design was applied in this study. A total of 575 patients diagnosed with bronchoscopy and pathologic confirmed were enrolled from The First Clinical Medical College and The Affiliated Union Hospital of Fujian Medical University, and Fuzhou General Hospital. 575 healthy control subjects consisted of hospital visitors and community population. All the control subjects were frequency-matched to the cases on age(±3 years) and gender. Each participants was scheduled for a face-to-face interview with the structured questionnaire. About 5 ml blood was collected from each case and saliva was collected from each control by The Oragene DNA Self-Collection Kit.The genomic DNA was extracted from all blood and saliva samples. The polymorphisms of NBS1 were investigated by PCR-RFLP. EpiData 3.0 was used to collect and SPSS 13.0 for windows to analyse the data, except PHASE 2.1 software to estimate haplotype frequencies and dihaplotypes.[Results]1. The major risk factors of lung cancer included: smok over 30 pack-year (OR=5.741,95%CI=3.579-9.207), second-hand smoke at home(OR=1.846, 95%CI =1.333-2.556), second-hand smoke at work(OR=4.150, 95%CI=2.917-5.904), kitchen fumes(10 years before)(OR=1.972,95%CI=1.267-3.069), unseparate kitchen(10 years before)(OR=3.019, 95%CI=1.142-7.981), strong smell after decorated(OR=2.125, 95%CI=1.341-3.368), polluted factory near the living place(OR=1.829,95%CI= 1.188-2.814), drinking spirit(≦38℃)(OR=2.537, 95%CI=1.115-5.773),use fertilizer pesticide(OR=2.474,95%CI=1.648-3.716), introversive character(OR=1.892, 95%CI= 1.090-3.283), BMI﹤18.5(OR=2.576,95%CI=1.451- 4.573).The protective factors of lung cancer included: BMI≧25(OR=0.571, 95%CI= 0.388-0.841), easy work(OR=0.614, 95%CI=0.424-0.890), walking(10 years before) (OR=0.539,95%CI=0.359-0.808), drinking tea(OR=0.457, 95%CI=0.284-0.735), eating eggs(﹥3次/周)(OR=0.382,95%CI=0.210-0.694), and fresh fruits(﹥3次/周)(OR=0.205, 95%CI=0.114-0.368).2. We found combined effects of smoking and tea drinking, as well as fresh fruits consumption.3. The analysis of NBS1 polymorphisms with susceptibility to lung cancer showed that the SNP rs1805794 alleles was significantly associated with a increased risk of lung cancer (C/G + G/G versus C/C: OR=1.461;95%CI=1.085-1.961).We did not find association between the SNP rs2735383 alleles and lung cancer.4. Haplotype frequencies analysis revealed that a increased risk of developing lung cancer was observed for Hap4-GC(OR=1.695, 95%CI=1.243-2.313), compared with Hap1-CG .5. Dihaplotypes analysis revealed that individuals with GC/GG dihaplotype have a 1.746-fold (95%CI=1.106-2.756) excess risk of developing lung cancer, compared with individuals for the GG/CC dihaplotype.6. There were combined effects between NBS1and smoking, or fresh fruits consumption.[Conclusion]1. Smoking,second-hand smoking, kitchen fumes, unseparate kitchen, fertilizer pesticide exposure, BMI﹤18.5 ,and so on,were the main risk factors of lung cancer.2. The results suggested that NBS1 polymorphisms were associatied with lung cancer.3. There were combined effects in etiology of lung cancer between NBS1 polymorphisms and environmental factors such as smoking.