Combined effects of cigarette smoking, DNA methyltransferase 3B genetic polymorphism, and DNA damage on lung cancer

Abstract

Background 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. 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. Methods Questionnaires 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. Results The 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. Conclusions Our 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.

Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status

“…CS is implicated in inducing hypermethylation mechanism via increasing the expression of DNA methyl transferase enzymes (DNMTs) [ 42 , 43 ]. The possible mechanism could be through DNA damage on DNMT3b which occurs as a result of the existences of carcinogens content in CS including arsenic, formaldehyde, and nitrosamines [ 44 ], leading to a transition from C to T that is located on the promoter 149 bp away from the transcription start site; it was revealed that nonsmokers harbor DNMT3b –149 CT genotype while smokers contain DNMT3b –149 TT genotype [ 42 ]. Consequently, an increase of DNMT3b activity is observed, causing an establishment of de novo methylation of CpG on some tumor suppressor genes [ 45 ].…”

Evaluation of Cellular Changes and Immunohistochemistry Expression of p53 and p16 in the Oral Mucosa Among Saudi Smokers

“…For example, Sunberg et al [7] found a significant increase in P16 expression among smokers compared to nonsmokers in oral squamous cell carcinoma. Similarly, Liu et al [11] reported a positive correlation between smoking and p53 overexpression in oral leukoplakia [12,13].…”

“…For example, Sunberg et al [ 7 ] found a significant increase in P16 expression among smokers compared to nonsmokers in oral squamous cell carcinoma. Similarly, Liu et al [ 11 ] reported a positive correlation between smoking and p53 overexpression in oral leukoplakia [ 12 , 13 ]. The current study investigated the cellular alterations and the immunohistochemical expression of p53 and p16 in the oral mucosa among smokers in Saudi Arabia.…”