吸烟相关性喉癌遗传易感基因的初步研究

doi:10.19401/j.cnki.1007-3639.2018.01.002

中国癌症杂志 ›› 2018, Vol. 28 ›› Issue (1): 11-21.doi: 10.19401/j.cnki.1007-3639.2018.01.002

吸烟相关性喉癌遗传易感基因的初步研究

朱奕¹，郭荦²，王胜资¹

1. 复旦大学附属眼耳鼻喉科医院放疗科，上海 200031 ；
2. 复旦大学附属眼耳鼻喉科医院实验中心，上海 200031

出版日期:2018-01-30 发布日期:2018-02-07
通信作者: 王胜资　E-mail：shengziwang@fudan.edu.cn
基金资助:
喉癌综合防治的研究(SHDC12012317)。

A preliminary study of genetic susceptibility to smoking-related laryngeal carcinoma

ZHU Yi¹, GUO Luo², WANG Shengzi¹

1. Department of Radiation Oncology, Shanghai Eye and ENT Hospital of Fudan University, Shanghai 200031, China; 2. Department of Experiment Center, Shanghai Eye and ENT Hospital of Fudan University, Shanghai 200031, China

Published:2018-01-30 Online:2018-02-07
Contact: WANG Shengzi E-mail: shengziwang@fudan.edu.cn

摘要/Abstract

摘要： 背景与目的：烟草成分经吸烟在进入人体后造成机体基因异常从而导致肿瘤的发生，然而并非所有暴露于吸烟这一高危因素下的人群都会罹患恶性肿瘤，肿瘤除了有家族聚集现象外，不同个体或种系对促进肿瘤发生的环境因素也存在差异。该研究旨在通过对目标基因及其单核苷酸多态性(single nucletide polymorphism，SNP)片段的检测分析，了解其基因型及等位基因与吸烟相关性喉癌发生的相关性，寻找与喉癌发生相关的遗传易感基因，为喉癌的早期预防及检测起到预警作用。方法：分别采集经复旦大学附属眼耳鼻喉科医院治疗的喉癌患者94例及高危吸烟人群148例的外周血血样(所有入组者的吸烟指数均大于400/年支)，对所有的外周血样进行DNA抽提。根据文献报道的前期研究结果选取与吸烟相关性肿瘤发生密切相关的候选基因，分别为ERCC5、CYP1A1、OGG1、RAD51、ERCC1、MMP2和MMP3；并进一步在基因库选取其SNP片段，采用Sequenom SNP检测技术完成对基因片段的检测。结果：N分期及临床分期与吸烟程度明显相关(P<0.05)。MMP2基因的rs243865片段及MMP3基因的rs522616片段分别得到了统计学阳性的结果(P<0.05)。根据吸烟指数分层分析后认为，重度吸烟人群中ERCC1的rs2298881位点GT基因型携带者，其罹患喉癌风险显著升高(P=0.025)。结论：吸烟促进喉癌进展；MMP2的rs243865片段及MMP3的rs522616片段可能是吸烟相关性喉癌的遗传易感基因的SNP；ERCC1的rs2298881片段在重度吸烟人群中具有一定的临床意义。

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

朱奕,郭荦,王胜资. 吸烟相关性喉癌遗传易感基因的初步研究[J]. 中国癌症杂志, 2018, 28(1): 11-21.

ZHU Yi, GUO Luo, WANG Shengzi. A preliminary study of genetic susceptibility to smoking-related laryngeal carcinoma[J]. China Oncology, 2018, 28(1): 11-21.

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吸烟相关性喉癌遗传易感基因的初步研究

A preliminary study of genetic susceptibility to smoking-related laryngeal carcinoma

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