DNA Methyltransferase 3B -149 Genetic Polymorphism Modulates Lung Cancer Risk Elicited By Smoking

Chia-Chen HUANG, , Taiwan (ROC)
LAI C. 2,3 , TSAI C. 4,5 , WANG J. 2,6 , CHEN Y. 1 , CAI Y. 1 , WONG R. 1,2,7

1 Department of Public Health, Chung Shan Medical University, Taichung, Taiwan
2 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
3 Thoracic Surgery, Cheng Ching General Hospital, Taichung, Taiwan
4 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan
5 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
6 Department of Family Medicine, Cheng Ching General Hospital, Taichung, Taiwan
7 Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

Cigarette smoking can increase stability of DNA methylation, hypermethylation of tumor suppressor genes, and sensitivity for carcinogens, thus subsequently lung cancer will be developed. DNA methyltransferase 3B (DNMT3B) is the key methyltransferase in DNA methylation regulation. Especially, green tea might lower incidence of cancer through the inhibition of DNA methyltransferase activity. Here, we designed a hospital-based case-control study to evaluate the influence of smoking, green tea consumption, and genetic polymorphism of DNMT3B -149 on the risk of lung cancer. A total of 190 lung cancer patients and 380 healthy controls were collected in this study. Questionnaires were administered to obtain demographic data, smoking status, green tea consumption, vegetables and fruits intake, exposure to fumes of cooking, and family history of lung cancer. Genotypes for DNMT3B -149 were identified by polymerase chain reaction. Results showed smoking, green tea consumption, exposure to fumes of cooking, family history of lung cancer, and polymorphism of DNMT3B -149 were significantly associated with development of lung cancer. Compared with nonsmokers who carrying DNMT3B -149 CT genotype, smokers who carrying DNMT3B -149 TT genotype had a higher odds ratio of 2.89 (95% C.I. = 1.17-7.12), and the interaction of smoking with DNMT3B -149 genotype on the risk of lung cancer was statistically significant. However, the test for the interaction between green tea consumption and DNMT3B -149 genotype on lung cancer risk was not significant. Our results suggested that DNMT3B -149 TT genotype with higher promoter activity might increase lung cancer risk elicited by smoking.