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: Yongtang Jin, Peiwei Xu, Xinneng Liu, Chunye Zhang, Cong Tan, Chunmei Chen, Xiaoyu Sun, Yingchun Xu
• Journal: Cancer investigation (Cancer Invest) Vol. 34 Issue 4 Pg. 173-80 ( 2016) ISSN: 1532-4192 [Electronic] England
• PMID: 27042875 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Adducts
• benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA
• 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Topics

• 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide (metabolism)
• Adult
• Aged
• Asian People (genetics)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism)
• DNA Adducts (genetics, metabolism)
• DNA Methylation
• Female
• Genes, Tumor Suppressor
• Humans
• Lung Neoplasms (genetics, metabolism)
• Male
• Middle Aged
• Promoter Regions, Genetic
• Smoking (genetics, metabolism)