Zhu Yi, Guo Luo, Wang ShengZi, Yu Qun, Lu JianXiong
Department of Radiation Oncology of Shanghai Eye and ENT Hospital of Fudan University, Shanghai, 200031, China.
Department of Experiment centre of Shanghai Eye and ENT Hospital of Fudan University, Shanghai,200031, China.
J Cancer. 2018 Feb 28;9(6):968-977. doi: 10.7150/jca.22841. eCollection 2018.
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/dayyear.) 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/dayyear (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.
一项调查纳入了200例来自眼耳鼻喉医院且经病理确诊的吸烟相关喉癌患者以及190例高危吸烟者。所有参与者的吸烟指数均大于400（香烟/日×年）。我们获取了临床和基线特征数据，并采集外周血进行DNA提取，以分析吸烟与喉癌发生之间的相关性。我们选择了在初步研究中发现与吸烟相关肿瘤密切相关的候选基因和单核苷酸多态性（SNP）片段。所选的候选基因有XPG、CYP1A1、OGG1、ERCC5、ERCC1、MMP2和MMP9。然后我们使用Sequenom SNP检测技术进行SNP测序。对目标基因和单核苷酸多态性（SNP）片段进行评估，以分析基因型或等位基因与吸烟相关喉癌之间的相关性，并确定与喉癌相关的易感基因。结果包括四项主要发现：（1）喉癌患者与对照受试者之间的吸烟指数存在显著差异（P = 0.0035）。吸烟指数大于600香烟/日×年的个体患喉癌的风险增加（P = 0.03）。（2）吸烟指数与T、N分期及临床分期显著相关（P < 0.05）。（3）CYP1A1的多态性位点rs1048943、rs4646421和rs4646422以及MMP9的多态性位点rs17577与喉鳞状细胞癌显著相关（P < 0.05）。（4）按吸烟程度对受试者进行分层后，ERCC1的rs2298881位点的GT基因型在重度吸烟者中与患喉癌的风险显著增加相关（P = 0.04）。结果表明，吸烟在喉鳞状细胞癌的发生和发展中起重要作用；CYP1A1和MMP9可能是吸烟相关喉癌的易感基因SNP，而ERCC1可能在重度吸烟者中起重要作用。本研究结果可能有助于识别用于检测和预防喉癌的早期标志物。
