[Association between polymorphism in notch signaling pathway and lung cancer risk]

Objective: To analyze the relationship between single nucleotide polymorphisms (SNP) of Notch signaling pathway and susceptibility to lung cancer. Methods: The present study was a hospital-based case-control study. All 1 121 patients of lung cancer diagnosed by histopathology three hospitals in Fujian and Nanjing were selected as cases from January 2006 to December 2012. At the same time, 1 121 healthy population from other departments of the hospital to visit patients or community, excluding those with tumor, chronic disease, and immediate family members of lung cancer, were enrolled in control group. A uniform questionnaire was used to collect general information. Matrix-assisted laster desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify the polymorphisms of 9 SNP (Notch3 rs3815188, Notch4 rs915894, Notch4 rs520692, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637, HES2 rs11364) in 1 121 lung cancer patients and 1 121 healthy controls. The association between SNP and lung cancer was analyzed by χ(2) and logistic regression model. Results: The average age of cases and controls was (58.70±10.73) and (58.98±10.85) years old. The OR for genotype AC carriers of HEY1 rs1046472 was 0.80 (95%CI: 0.66-0.97) when comparing with genotype CC. The OR for genotype AC+AA carriers of HEY1 rs1046472 was 0.81 (95% CI: 0.67-0.98) when comparing with genotype CC. The OR for genotype AC carriers of HEY2 rs3734637 was 0.82 (95%CI: 0.67-0.99) when comparing with genotype AA. In the stratified analysis, Notch3 rs3815188, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637, HES2 rs11364 were associatied with the risk of lung cancer, P were 0.041, 0.030, 0.043, 0.003, 0.004, 0.026 and 0.038, respectively.The interactions analysis done by logistic regression model showed JAG1 rs8708 and family history, JAG2 rs9972231 and BMI had interaction in the study, OR were 2.07 (95% CI:1.21-3.52) and 1.73 (95% CI:1.21-2.47), respectively. Conclusion: Notch3 rs3815188, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637 and HES2 rs11364 were significantly associated with susceptibility to lung cancer.