Abstract

BackgroundSmoking increases DNA methylation and DNA damage, and DNA damage acts as a vital cause of tumor development. The DNA methyltransferase 3B (DNMT3B) enhances promoter activity and methylation of tumor suppressor genes. Tea polyphenols may inhibit DNMT activity. We designed a case-control study to evaluate the combined effects of smoking, green tea consumption, DNMT3B − 149 polymorphism, and DNA damage on lung cancer occurrence.MethodsQuestionnaires were administered to obtain demographic characteristics, life styles, and family histories of lung cancer from 190 primary lung cancer cases and 380 healthy controls. Genotypes and cellular DNA damage were determined by polymerase chain reaction and comet assay, respectively.ResultsThe mean DNA tail moment for lung cancer cases was significantly higher than that for healthy controls. Compared to nonsmokers carrying the DNMT3B − 149 CT genotype, smokers carrying the TT genotype had a greater lung cancer risk (odds ratio [OR]: 2.83, 95% confidence interval [CI]: 1.62–4.93). DNA damage levels were divided by the tertile of the healthy controls’ values. Compared to nonsmokers with low DNA damage, smokers with moderate DNA damage (OR: 2.37, 95% CI: 1.54–3.63) and smokers with high DNA damage (OR: 3.97, 95% CI: 2.63–5.98) had elevated lung cancer risks. Interaction between smoking and DNA damage significantly affected lung cancer risk.ConclusionsOur study suggested that the DNMT3B − 149 TT genotype, which has higher promoter activity, can increase the lung cancer risk elicited by smoking, and DNA damage may further promote smoking related lung cancer development.

Highlights

  • Smoking increases DNA methylation and DNA damage, and DNA damage acts as a vital cause of tumor development

  • Participant characteristics In total, 570 participants were recruited in this study (60.5% for males and 39.5% for females), and the characteristics of this study participants are summarized in DNA tail moment of lung cancer patients and controls Table 2 shows the mean DNA tail moment of each peripheral blood cell with stratification of specific characteristics in lung cancer patients and controls

  • The tail moment was not associated with various factors in lung cancer cases

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Summary

Introduction

Smoking increases DNA methylation and DNA damage, and DNA damage acts as a vital cause of tumor development. The DNA methyltransferase 3B (DNMT3B) enhances promoter activity and methylation of tumor suppressor genes. We designed a case-control study to evaluate the combined effects of smoking, green tea consumption, DNMT3B − 149 polymorphism, and DNA damage on lung cancer occurrence. Evidence shows that smoking can increase DNA methylation and DNA damage [3, 4]. These may be the crucial mechanisms of smoking related lung cancer. DNA damage has been proposed as a vital cause of cancer occurrence and development [11]. Any condition leading to high levels of DNA damage, if not repaired, may potentially result in carcinogenic effects [11]

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