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吸烟与NQO1基因C609T多态性对北非人群未分化鼻咽癌风险的联合影响。

Joint effect of smoking and NQO1 C609T polymorphism on undifferentiated nasopharyngeal carcinoma risk in a North African population.

作者信息

Moumad Khalid, Khaali Wafa, Benider Abdellatif, Ben Ayoub Wided, Hamdi-Cherif Mokhtar, Boualga Kada, Hassen Elham, Ben Driss El Khalil, Corbex Marilys, Khyatti Meriem

机构信息

Oncovirology Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.

Departement of Biology, Faculty of Sciences, Abdelmalek Essaadi University, Tetouan, Morocco.

出版信息

Mol Genet Genomic Med. 2018 Nov;6(6):933-940. doi: 10.1002/mgg3.461. Epub 2018 Aug 29.

DOI:10.1002/mgg3.461
PMID:30160047
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6305636/
Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) has a higher incidence in North Africa than in most parts of the world. In addition to environmental factors such as Epstein-Barr virus infection and chemical carcinogen exposure, genetic susceptibility has been reported to play a key role in the development of NPC. NAD(P)H: quinone oxidoreductase 1 is a cytosolic enzyme that protects cells from oxidative damage. A C to T transition at position 609 in the NQO1 gene (OMIM: 125860) has been shown to alter the enzymatic activity of the enzyme and has been associated with increased risk to several cancers. This study investigates for the first time the effect of this polymorphism on NPC susceptibility in a North African population.

METHODS

The NQO1 C609T polymorphism was genotyped using PCR-RFLP in 392 NPC cases and 365 controls from Morocco, Algeria, and Tunisia.

RESULTS

The allele frequencies and distributions of genotypes did not differ between cases and controls (p > 0.05). When stratifying according to smoking status, we observed two-fold higher NPC risk in ever-smokers carrying the CT or TT genotype. Multiple logistic regression analysis revealed that there was a significant interaction between T allele and smoking status (OR = 1.95, 95% CI = 1.20-3.19; interaction p = 0.007).

CONCLUSION

In this North African population, the functional NQO1 polymorphism was associated with a significantly higher risk of NPC among smokers and did not affect the risk among nonsmokers.

摘要

背景

鼻咽癌(NPC)在北非的发病率高于世界上大多数地区。除了诸如爱泼斯坦-巴尔病毒感染和接触化学致癌物等环境因素外,据报道遗传易感性在鼻咽癌的发生发展中起关键作用。NAD(P)H:醌氧化还原酶1是一种胞质酶,可保护细胞免受氧化损伤。已证明NQO1基因(OMIM:125860)第609位的C到T转换会改变该酶的酶活性,并与多种癌症的风险增加有关。本研究首次调查了这种多态性对北非人群鼻咽癌易感性的影响。

方法

采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对来自摩洛哥、阿尔及利亚和突尼斯的392例鼻咽癌患者和365例对照进行NQO1 C609T多态性基因分型。

结果

病例组和对照组的等位基因频率和基因型分布无差异(p>0.05)。按吸烟状况分层时,我们观察到携带CT或TT基因型的曾经吸烟者患鼻咽癌的风险高出两倍。多因素logistic回归分析显示,T等位基因与吸烟状况之间存在显著交互作用(比值比[OR]=1.95,95%置信区间[CI]=1.20-3.19;交互作用p=0.007)。

结论

在这个北非人群中,功能性NQO1多态性与吸烟者患鼻咽癌的风险显著升高相关,而对不吸烟者的风险没有影响。

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