Lack of association between Caucasian lung cancer risk and O6-methylguanine-DNA methyltransferase-codon 178 genetic polymorphism

BACKGROUND: The presence of nicotine metabolite in the urine of subjects exposed to tobacco smoke represents the nicotine metabolism activity in environmental tobacco smokers. CYP2A6 and CYP2A13 are known as the main enzymes responsible for nicotine metabolism and xenobiotic activity in tobacco smoke-related lung cancer. AIM: The aim of this study is to analyze the relationship between genetic polymorphism of CYP26 and CYP2A13 genes and environmental tobacco smoke-induced lung cancer risk in Indonesian females never smoker. METHODS: This is a case-control study with two-stage of distinguishing polymorphism detection. Restriction fragment length polymorphism polymerase chain reaction from venous blood extraction was performed to examine the CYP2A6 and CYP2A13 polymorphism. Logistic regression test in Epi Info-7 software was carried out to examine genetic polymorphism of CYP2A6 and CYP2A13 genes and environmental tobacco smoke-induced lung cancer risk in Indonesian female never smokers. RESULTS: A total of 203 participants enrolled in this study with the first stage of CYP2A6 polymorphism involved 101 subjects showed no significant correlation between the genotypes of CYP2A6 and the incidence of lung cancer. On the other hand, there was a significant correlation between genotypes of CYP2A13 and the incidence of lung cancer (p < 0.05). People with the genotype CT have a 2.7 higher risk for developing lung cancer compare with genotype CC. Allele *1B was the most common allele in CYP2A6. Allele C has more frequencies and has 0.62 times the risk for developing lung cancer compared with allele T with a wide range of confidence intervals (0.73–3.52). CONCLUSIONS: There was a significant correlation between polymorphism CYP213 with the incidence of lung cancer among female lung cancer never smoker. However, the results show no significant relationship between CYP2A6 genetic polymorphism and lung cancer incidence.

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

BMC Cancer ◽

10.1186/s12885-021-08800-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chia-Chen Huang ◽

Chung-Yu Lai ◽

Chin-Hung Tsai ◽

Jiun-Yao Wang ◽

Ruey-Hong Wong

Keyword(s):

Lung Cancer ◽

Dna Damage ◽

Cancer Risk ◽

Dna Methyltransferase ◽

Promoter Activity ◽

Lung Cancer Risk ◽

Primary Lung Cancer ◽

Healthy Controls ◽

Combined Effects ◽

Dna Methyltransferase 3B

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.

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