Abstract: Background and purpose: Tobacco leads to the occurrence of cancer caused by genetic mutations, but not all people exposed to smoking will suffer from malignant tumors. In addition to family aggregation phenomenon, the discrepancy exists between individuals or species to promote tumor with environmental factors. We obtained clinical data from laryngeal carcinoma patients and analyzed the correlation between smoking and the occurrence of laryngeal carcinoma. Target genes and single nucleotide polymorphism (SNP) fragments were evaluated to analyze the correlation between genotype or allele and smoking-related laryngeal carcinoma, and to identify susceptibility genes related to laryngeal carcinoma. This information may help identify an early marker for the detection and prevention of laryngeal carcinoma. Methods: A total of 94 smoking-related laryngeal carcinoma patients who were pathologically confirmed and treated at Shanghai Eye and ENT Hospital of Fudan University as well as 148 high-risk smokers were included in the survey. All participants had a smoking index greater than 400 pieces/year. We collected clinical data and baseline materials. Peripheral blood was obtained for DNA extraction, and Sequenom SNP detection technology was used to assess relationships with DNA sequencing fragments. We selected candidate genes and SNP fragments that were closely associated with smoking-related tumors based on preliminary studies. The genes included ERCC5, CYP1A1, OGG1, RAD51, ERCC1, MMP2 and MMP3. Results: N stage and clinical stage exhibited a significant correlation with the smoking index (P<0.05). MMP2-rs243865 and MMP3-rs522616 showed significantly different expressions between carcinoma cases and controls (P<0.05). Analysis based on stratification of the smoking index indicated that the GT genotype of ERCC1-rs2298881 significantly increased the risk of laryngeal carcinoma in heavy smokers (P=0.025). Conclusion: Smoking promotes the occurrence and development of laryngeal carcinoma. MMP2-rs243865 and MMP3-rs522616 are susceptibility SNP for smoking-related laryngeal carcinoma, and ERCC1-rs2298881 plays an important role in the development of laryngeal carcinoma in heavy smokers.

Key words: Laryngeal carcinoma, Smoking-related, Genetic susceptibility, Single nucleotide polymorphism, MMP2, MMP3, ERCC1