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Objective To study the base sequence mutations in exons 18-21 of epidermal growth factor receptor (EG­FR) gene in the cancer tissues of patients with non-small-cell lung cancer ( NSCLC). Methods The specimens of cancer tissues from 72 NSCLC patients were preserved during the operation. Another 20 specimens of normal lung tissues were col­lected as the controls. The sequences of EGFR exons 18-21 in the cancer tissues and normal lung tissues were detected by direct sequencing. The EGFR mutations were analyzed. We compared the type of base mutation with NCBIs EGFR clinical gene mutation database ( ClinVar) to determine whether the sample mutation type was a pathological mutation and whether it corresponded to a specific drug response type. In addition， we analyzed the relationship between EGFR gene mutations and clinicopathological features of patients with NSCLC. Results The mutation rates of EGFR exons 18-21 in the NSCLC cancer tissues and normal tissues were 58.3% (42/72) and 0，respectively，with significant difference (P <0. 05). Mutations were found in all 4 exons. Sixty specific mutations were found in the detected exons of EGFR. The mutation types included point mutation，deletion mutation，insertion mutation，and insertion/deletion mutation. The mutation rates of ex­ons 18-21 were 8.3% (6/72) , 29.2% (21/72) , 37.5% (27/72) , and 4.2% (3/72) , respectively. Each exon had specific mutation types. There were 4 , 21 , 9 and 1 point mutations in exons 18-21 , respectively. Other specific mutations included 13 insertion/deletion mutations in exon 19 , 2 deletion and 1 insertion/deletion mutations in exon 20 , and 1 inser­tion mutation in exon 21. There were 6 cancer-associated mutations in this study , including 1 benign variation ( c. 2361G > A) with mutation rate of 31. 9% (23/72)，1 drug-sensitive mutation ( c. 2830T > G) with mutation rate of 2. 8% (2/ 72) , and 4 carcinogenic mutations. The overall rate of cancer-associated mutations was 12. 5% (9/72). The targeted drug-sensitive mutations got an overall rate of 2. 8% (2/72) . The mutation of c. 2573T > G in exon 21 caused Leu858Arg variation, which was a sensitive mutation in EGFR-targeted drug therapy. Conclusion There is a high mutation rate of EGFR exons 18-21 in NSCLC cancer tissues. The main mutation types are point mutation, deletion mutation, insertion mu­tation and insertion ／ deletion mutation. Exon 19 has the most mutations，and the mutations of exon 20 are the most com­plex. Of the 6 cancer-associated mutations，only one targeted drug-sensitive mutation is found in exon 21 . [ABSTRACT FROM AUTHOR]

Objective To analyze the relationship between single nucleotide polymorphisms (SNP) of Notch1 gene rs3124599 and susceptibility to lung cancer in patients with primary lung cancer. Methods A total of 78 patients with primary lung cancer (observation group) and 156 healthy subjects (control group) were enrolled. The morning venous blood of the two groups were taken (2 m L). DNA was extracted by phenol-chloroform extraction and Notch1 gene rs3124599 locus typing was analyzed by PCR-PFLPS technique. The clinical data of the two groups were collected. The correlation between various factors and susceptibility to lung cancer was evaluated by conditional logistic regression analysis. The interaction coefficient (γ) was used to evaluate the interaction between environmental factors and gene polymorphism. Results The distribution frequencies of Notch1 gene rs3124599 genotypes AA,AG,GG in the observation group were 25.6% (20/78),39.7% (31/78),and 34.6% (27/78),which were 37.2% (58/156),44.9% (70/156),and 17.9% (28/156) in the control group; the distribution frequencies of alleles A and G in the observation group were 45.5% (71/156)and 54.5% (85/156),respectively,which were 59.6% (186/312) and 40.4% (126/312) in the control group. The differences of the distribution of genotypes and alleles A and G between the two groups were statistically significant (χ2=6.518,3.987; all P < 0.05). The number of smoking,degree of smoking,and the family history of cancer in the observation group were higher than those in the control group (χ2= 23.890,5.647; P < 0.05). Conditional logistic regression analysis showed that individuals with rs3124599 GG genotype had an increased risk of lung cancer as compared with individuals with rs3124599 AA genotype (corrected OR = 1.596,95% CI: 1.058-2.429). The individuals carrying alleles G gene were 1.193 times more likely to develop lung cancer than those carrying A gene (95% CI: 1.132 to 2.501,P <0.05). The rs3124599 locus AG or GG genotype had positive interaction with smoking (γ = 2.296) and drinking (γ =1.130). When the rs3124599 locus AG/GG genotype was associated with a family history of the tumor,the risk of developing lung cancer increased (OR = 3.751,95% CI = 1.665-18. 034). Compared with rs3124599 genotype AA non-smokers,the risk of lung cancer in smokers or smokers carrying AG/GG increased by 4.495 times and 12.134 times,respectively. Conclusion The mutation frequency of allele G in Notch1 gene rs3124599 is higher in lung cancer patients. The allele G of the Notch1 gene rs3124599 (A/G) may be a risk factor for lung cancer,and it has an interaction with the patient’s family history of cancer and smoking history. [ABSTRACT FROM AUTHOR]