The Association Study Of DNA Double-strand Break Repair Genes BRCA1,BRCA2 And NBS1 Polymorphisms With Susceptibility To Molecular Epidemiology Of Lung Cancer

[Objective]To explore the environmental risk factors of lung cancer and the association of DNA double-strand break repair genes BRCA1,BRCA2 and NBS1 polymorphisms with susceptibility to lung cancer, and the combined effects in the development of lung cancer.[methods]A case-control design was applied in this study. A total of 781 patients diagnosed with bronchoscopy and pathologic confirmed were recruited from The First Clinical Medical College and The Affiliated Union Hospital of Fujian Medical University, and Fuzhou General Hospital.781 healthy control subjects consisted of hospital visitors and community population. All the control subjects were frequency-matched to the cases on age (±1 years) and gender. Each participant was scheduled for a face-to-face interview with a structured questionnaire. About 5 ml blood was collected from each case and saliva was collected from each control by Oragene DNA Self-Collection Kit. The genomic DNA was extracted from all blood and saliva samples. The polymorphisms of BRCA1,BRCA2 and NBSl were determined by PCR-RFLP. EpiData 3.0 was used to build database and SPSS 13.0 for windows to analyse the data, except Haplostata and PHASE 2.0 software to estimate haplotype frequencies and dihaplotypes, and MDR 1.0.0 software for transactional analysis.[Results]l.The major risk factors of lung cancer included:contaminative factory around residential (OR=1.815,95%CI=1.283-2.569), insufficient residential ventilation (OR=1.905,95%CI=1.344-2.699), heavy smoke during cooking (OR=2.246, 95%CI=1.196-4.218), living in bungalow (OR=1.375,95%CI=1.054-1.795), long duration of irritant smell (OR=1.860,95%CI=1.227-2.819), smoke (>30 pack-years) (OR=5.410,95%CI=3.778-7.748), second-hand smoke at home (OR=1.711, 95%CI=1.319-2.220), second-hand smoke at work (OR=3.691,95%CI=2.799-4.867), peasant career (OR=1.589,95%CI=1.172-2.154), BMI<18.5 (OR=2.578, 95%CI=1.637-4.059). The protective factors of lung cancer included:BMI= 25 (OR=0.630, 95%CI=0.470-0.845), drinking tea (OR=0.635,95%CI=0.492-0.820).2. The best combined effects were found between smoke during cooking, smoking,second-hand smoke at home and second-hand smoke at work.In the non-smoking people,second-hand smoke at home is the main risk factor of lung cancer.3. There was a negative linear correlation between BMI and lung cancer risk.4. The analysis of BRCA2 polymorphisms with susceptibility to lung cancer showed that the SNP rs144848 alleles was significantly associated with a decreased risk of lung cancer (C/G+G/G versus C/C:OR=0.726; 95%CI=0.583-0.905).And no association between the SNP rs16942 alleles in BRCA1, SNP rs 1805794, rs2735383 in NBS1 and lung cancer observed.5. Haplotype frequencies analysis revealed that a increased risk of developing lung cancer for individuals with Hap4-GC (OR=0.46,95%CI=1.14-1.89), compared with Hap1-CG.6. Dihaplotypes analysis suggested that individuals with GC/GC dihaplotype have a 2.389-fold (95%CI=1.752,3.258) excess risk of developing lung cancer, compared with individuals for the GG/CC dihaplotype.7. There were combined effects between BRCA1,BRCA2,NBS1and smoking.8. Comparing with gene, environmental/behavior factors take a main role in developing lung cancer.[Conclusion]1. Smoking, second-hand smoking, contaminative factory around residential, BMI<18.5,and so on were the main risk factors of lung cancer.Drinking tea and BMI>25 are protective factors of lung cancer.2. The results suggested that BRCA2 and NBS1 polymorphisms were associated with lung cancer.3. Compared with gene, environmental factors take a main role in developing lung cancer.