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口腔癌前病变病例中线粒体C序列改变与烟草暴露之间的关联。

Association between mitochondrial C-tract alteration and tobacco exposure in oral precancer cases.

作者信息

Pandey Rahul, Mehrotra Divya, Mahdi Abbas Ali, Sarin Rajiv, Kowtal Pradnya, Maurya Shailendra S, Parmar Devendra

机构信息

Department of Oral and Maxillofacial Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India.

Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India.

出版信息

Natl J Maxillofac Surg. 2013 Jul;4(2):219-24. doi: 10.4103/0975-5950.127655.

Abstract

INTRODUCTION

Tobacco exposure is a known risk factor for oral cancer. India is home to oral cancer epidemic chiefly due to the prevalent use of both smoke and smokeless tobacco. To reduce the related morbidity early detection is required. The key to this is detailing molecular events during early precancer stage. Mitochondrion is an important cellular organelle involved in cell metabolism and apoptosis. Mitochondrial dysfunction is thought to be the key event in oncogenesis. Last decade has seen a spurt of reports implicating mitochondrial mutations in oral carcinogenesis. However, there are few reports that study mitochondrial deoxyribonucleic acid (mtDNA) changes in oral precancer. This study aims to understand and link effect of tobacco exposure on mtDNA in oral precancer cases.

SUBJECTS AND METHODS

A total of 100 oral precancer cases of which 50 oral leukoplakia and 50 oral submucous fibrosis were recruited in the study and a detailed questionnaire were filled about the tobacco habits. Their tissue and blood samples were collected. Total genomic DNA was isolated from both sources. Mitochondrial C-tract was amplified and bidirectional sequencing was carried out. Mutations were scored over matched blood DNA.

RESULTS

There was a significant association between the presence of mitochondrial C-tract alteration and duration of tobacco exposure. The probability increased with increasing duration of tobacco consumption. The risk of having this alteration was more in chewers than in smokers.

CONCLUSIONS

Tobacco in both form, chewable and smoke, is oncogenic and causes early changes in mitochondrial genome and chances increases with increasing duration of tobacco consumption.

摘要

引言

烟草暴露是口腔癌已知的风险因素。印度是口腔癌流行的高发地区,主要原因是吸烟和无烟烟草的广泛使用。为降低相关发病率,需要进行早期检测。关键在于详细了解癌前早期阶段的分子事件。线粒体是参与细胞代谢和凋亡的重要细胞器。线粒体功能障碍被认为是肿瘤发生的关键事件。过去十年间,有大量报道表明线粒体突变与口腔癌发生有关。然而,很少有研究报道口腔癌前病变中线粒体脱氧核糖核酸(mtDNA)的变化。本研究旨在了解并关联烟草暴露对口腔癌前病变病例中线粒体DNA的影响。

研究对象与方法

本研究共纳入100例口腔癌前病变病例,其中50例口腔白斑和50例口腔黏膜下纤维化,并填写了关于烟草使用习惯的详细问卷。采集了他们的组织和血液样本。从这两种样本中分离出总基因组DNA。扩增线粒体C区域并进行双向测序。通过与匹配的血液DNA对比对突变进行评分。

结果

线粒体C区域改变的存在与烟草暴露时长之间存在显著关联。随着烟草消费时长的增加,这种可能性也会增加。咀嚼烟草者出现这种改变的风险高于吸烟者。

结论

可咀嚼和吸烟这两种形式的烟草都具有致癌性,会导致线粒体基因组早期变化,且随着烟草消费时长的增加,这种可能性也会增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5b8/3961899/a9fe672dfd71/NJMS-4-219-g002.jpg

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