J Cancer 2018; 9(6):968-977. doi:10.7150/jca.22841
Association of Smoking and XPG, CYP1A1, OGG1, ERCC5, ERCC1, MMP2, and MMP9 Gene Polymorphisms with the early detection and occurrence of Laryngeal Squamous Carcinoma
1. Department of Radiation Oncology of Shanghai Eye and ENT Hospital of Fudan University, Shanghai, 200031, China
2. Department of Experiment centre of Shanghai Eye and ENT Hospital of Fudan University, Shanghai,200031, China
3. Department of TianPing health service centre of Shanghai,Shanghai,200031,China
Zhu Y, Guo L, Wang S, Yu Q, Lu J. Association of Smoking and XPG, CYP1A1, OGG1, ERCC5, ERCC1, MMP2, and MMP9 Gene Polymorphisms with the early detection and occurrence of Laryngeal Squamous Carcinoma. J Cancer 2018; 9(6):968-977. doi:10.7150/jca.22841. Available from http://www.jcancer.org/v09p0968.htm
A total of 200 smoking-related laryngeal carcinoma patients with pathology confirmation from the Eye and ENT Hospital and 190 high-risk smokers were included in a survey. All of the participants had a smoking index greater than 400 (cigarettes/day*year.) We obtained data on clinical and baseline characteristics, and peripheral blood was obtained and subjected to DNA extraction to analyse the correlation between smoking and the occurrence of laryngeal carcinoma. We selected candidate genes and SNP fragments that were found to be closely associated with smoking-related tumours in preliminary studies. The selected candidate genes were XPG, CYP1A1, OGG1, ERCC5, ERCC1, MMP2, and MMP9. We then performed SNP sequencing using Sequenom SNP detection technology. Target genes and single nucleotide polymorphism (SNP) fragments were evaluated to analyse the correlation between genotype or allele and smoking-related laryngeal carcinoma and to identify susceptibility genes related to laryngeal carcinoma. The results included four main findings: (1) The smoking index differed significantly between laryngeal cancer patients and control subjects (P=0.0035). The risk of laryngeal cancer was increased among individuals with a smoking index greater than 600 cigarettes/day*year (P=0.03). (2) The smoking index was significantly correlated with the T, N and clinical stages (P<0.05). (3) The polymorphisms CYP1A1-rs1048943, rs4646421, and rs4646422 and MMP9-rs17577 were significantly associated with laryngeal squamous carcinoma (P<0.05). (4) After stratifying the subjects by smoking degree, the GT genotype of ERCC1-rs2298881 was associated with a significantly greater risk of laryngeal carcinoma among heavy smokers (P=0.04). The results suggest that smoking plays an important role in the occurrence and development of laryngeal squamous carcinoma; CYP1A1 and MMP9 might be susceptibility gene SNPs for smoking-related laryngeal carcinoma, and ERCC1 might play an important role in heavy smokers. The results of this study might help identify an early marker for the detection and prevention of laryngeal carcinoma.
Keywords: laryngeal squamous carcinoma, polymorphism, susceptibility genes, SNP, smoking