| Summary: | In tumor development, increased expression of DNA methyltransferase (DNMT) has been observed. In particular, cigarette smoke and tea polyphenols may influence <i>DNMT3B</i> mRNA expression by regulating microRNA (miR)-29b expression. Herein, we designed a case–control study to evaluate the joint effects of smoking and green tea consumption, with miR-29b and <i>DNMT3B</i> mRNA expression, in lung cancer development. A total of 132 lung cancer patients and 132 healthy controls were recruited to measure miR-29b and <i>DNMT3B</i> mRNA expression in whole blood. Results revealed that lung cancer patients had lower miR-29b expression (57.2 vs. 81.6; <i>p</i> = 0.02) and higher <i>DNMT3B</i> mRNA expression (37.2 vs. 25.8; <i>p</i> < 0.001) than healthy controls. Compared to non-smokers with both higher miR-29b and lower <i>DNMT3B</i> mRNA expression, smokers with both low miR-29b and higher <i>DNMT3B</i> mRNA expression had an elevated risk of lung cancer development (OR 5.12, 95% CI 2.64–9.91). Interactions of smoking with miR-29b or <i>DNMT3B</i> mRNA expression in lung cancer were significant. Interaction of green tea consumption with miR-29b expression and <i>DNMT3B</i> mRNA expression in lung cancer was also significant. Our study suggests that smokers and green tea nondrinkers with lower miR-29b expression and higher <i>DNMT3B</i> mRNA expression are more susceptible to lung cancer development.
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