title: Cigarette Smoking, BPDE-DNA Adducts, and Aberrant Promoter Methylations of Tumor Suppressor Genes (TSGs) in NSCLC from Chinese Population.
abstract: Non-small cell lung cancer (NSCLC) is related to the genetic and epigenetic factors. The goal of this study was to determine association of cigarette smoking and BPDE-DNA adducts with promoter methylations of several genes in NSCLC. Methylation of the promoters of p16, RARβ, DAPK, MGMT, and TIMP-3 genes of tumor tissues from 199 lung cancer patients was analyzed with methylation-specific PCR (MSP), and BPDE-DNA adduct level in lung cancer tissue was obtained by ELISA. Level of BPDE-DNA adduct increased significantly in males, aged people (over 60 years), and smokers; however, no significant difference was found while comparing the BPDE-DNA adduct levels among different tumor types, locations, and stages. Cigarette smoking was also associated with increased BPDE-DNA adducts level (OR = 2.43, p > .05) and increased methylation level in at least 1 gene (OR = 5.22, p < .01), both in dose-response manner. Similarly, cigarette smoking also significantly increase the risk of p16 or DAPK methylation (OR = 3.02, p < .05 for p16, and 3.66, p < .05 for DAPK). The highest risk of BPDE-DNA adducts was detected among individuals with cigarette smoking for more than 40 pack-years (OR = 4.21, p < .01). Furthermore, the present study did not show that BPDE-DNA adducts are significantly associated with abnormal TSGs methylations in NSCLC, including SCC and AdO, respectively. Conclusively, cigarette smoking is significantly associated with the increase of BPDE-DNA adduct level, promoter hypermethylation of p16 and DAPK genes, while BPDE-DNA adduct was not significantly related to abnormal promoter hypermethylation in TSGs, suggesting that BPDE-DNA adducts and TSGs methylations play independent roles in NSCLC.
authors.affiliation: a Department of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Yongtang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: a Department of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Peiwei
authors.initials: P
authors.lastname: Xu
authors.affiliation: a Department of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Xinneng
authors.initials: X
authors.lastname: Liu
authors.affiliation: a Department of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Chunye
authors.initials: C
authors.lastname: Zhang
authors.affiliation: a Department of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Cong
authors.initials: C
authors.lastname: Tan
authors.affiliation: a Department of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Chen
authors.affiliation: a Department of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Sun
authors.affiliation: b Institute of Pharmacology, Zhejiang University School of Pharmacology, Zhejiang University , Hangzhou , China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D018736:DNA Adducts / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000235:genetics* / Q000378:metabolism
chemical_list: D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
keywords: Cigarette smoking; DNA adduct; Gene methylation; Lung cancer