The DNA Methyltransferase 3B -149 Genetic Polymorphism Modulates Lung Cancer Risk from Smoking

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Smoking can cause increase of DNA methylation and hypermethylation of tumor suppressor genes, this possible contributing to subsequent lung cancer development. DNA methyltransferase 3B (DNMT3B) is crucial in regulation of DNA methylation and it has been proposed that green tea might lower cancer risk through inhibiting its activity. Here, we designed a case-control study to investigate whether the DNMT3B -149 genetic polymorphism could modulate lung cancer risk due to smoking. Possible interactions of smoking and green tea consumption with this DNMT3B genetic polymorphism were also assessed. </span></span><strong><span style="font-size: small;">Materials and Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">A total of 190 lung cancer patients and 380 healthy controls were recruited. Questionnaires were administered to obtain data on sociodemographic and lifestyle </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">variables, as well as family history of lung cancer. Genotypes for DNMT3B -149 were identified by polymerase chain </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">reaction. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Smoking, green tea consumption, exposure to cooking fumes, family history of lung cancer, and </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">the DNMT3B -149 genotype (odds ratio (OR)=2.65; 95% confidence interval (CI) 1.15-6.10) were all significantly </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">associated with the development of lung cancer. Smokers carrying the DNMT3B -149 TT genotype were at elevated risk compared to non-smokers carrying DNMT3B -149 (OR=7.69; 95% CI 2.55-23.14). Interaction of smoking with </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">DNMT3B -149 genotypes was significant regarding lung cancer risk. However, interaction between green tea drinking </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">and DNMT3B -149 genotypes was not. </span></span><strong><span style="font-size: small;">Conclusions: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">The DNMT3B -149 TT genotype might increase the smoking-associated lung cancer risk. </span></span>