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Association of Methylation of the RAR-β Gene with Cigarette Smoking in Non-Small Cell Lung Cancer with Southern-central Chinese Population

  • Li, Wen ;
  • Deng, Jing ;
  • Wang, Shuang-Shuang ;
  • Ma, Liang ;
  • Pei, Jiang ;
  • Zeng, Xiao-Xi ;
  • Tang, Jian-Xin
  • Published : 2015.01.22

Abstract

Pathogenesis of lung cancer is a complicated biological process including multiple genetic and epigenetic changes. Since cigarette smoking is confirmed as the most main risk factor of non-small cell lung cancer (NSCLC), the aim of this study was to determine whether tobacco exposure plays a role in gene methylation. Methylation of the RAR-${\beta}$ gene were detected using methylation-specific polymerase chain reaction in DNA from 167 newly diagnosed cases with NSCLC and corresponding 105 controls. A significant statistical association was found in the detection rate of the promoter methylation of RAR-${\beta}$ gene between NSCLC and controls ($x^2$=166.01; p<0.01), and hypermethylation of the RAR-${\beta}$ gene was significantly associated with smoking status (p=0.038, p<0.05). No relationship was found between RAR-${\beta}$ gene methylation and pathologic staging including clinical stage, cell type, gender and drinking (p>0.05), and the methylation of RAR-${\beta}$ gene rate of NSCLC was slightly higher in stages III+IV (80.0%) than in I+II (70.8%). Similar results were obtained for methylation of the RAR-${\beta}$ gene between squamous cell carcinoma (77.9%) and other cell type lung cancer (73.9%). These results showed that the frequency of methylation increased gradually with the development of clinical stage in smoking-associated lung cancer patients, and tobacco smoke may be play a potential role in RAR-${\beta}$ gene methylation in the early pathogenesis and process in lung cancer, particularly squamous cell carcinoma. Aberrant promoter methylation is considered to be a promising marker of previous carcinogen exposure and cancer risk.

Keywords

Methylation;non-small cell lung cancer;$RAR{\beta}$ gene;cigarette exposure

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  2. Association between nuclear expression of retinoic acid receptor alpha and beta and clinicopathological features and prognosis of advanced non-small cell lung cancer vol.21, pp.6, 2016, https://doi.org/10.1007/s10147-016-1002-0
  3. Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers vol.18, pp.6, 2017, https://doi.org/10.3390/ijms18061210
  4. Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation in Human Populations vol.39, pp.1, 2018, https://doi.org/10.1146/annurev-publhealth-040617-014629

Acknowledgement

Supported by : National Natural Science Foundation of China