title: The interaction of APEX1 variant with polycyclic aromatic hydrocarbons on increasing chromosome damage and lung cancer risk among male Chinese.
abstract: Polycyclic aromatic hydrocarbons (PAHs) are the most significant contributors to tobacco-induced lung carcinogenesis. Apurinic/apyrimidinic endonuclease 1 (APE1) is a central enzyme in the removal of apurinic/apyrimidinic sites caused by DNA damaging agents. This study aimed to investigate the potential interaction of APEX1 polymorphisms and PAHs on genetic damage and lung cancer risk among male Chinese. We recruited an occupational cohort of 922 male coke oven workers and determined their DNA damage levels by calculating the lymphocytic micronucleus (MN) frequencies. Two well-studied APEX1 polymorphisms (-307A > C and Asp148Glu) and their associations with MN frequencies were examined. The impact of MN-related single nucleotide polymorphism (SNP) on lung cancer risk was further investigated in two case-control studies including 1634 male lung cancer patients and 1678 controls. It was shown that, the APEX1 148Glu allele was associated with significantly higher MN frequencies than 148Asp allele, with strongest associations among the highest PAH-exposure workers (P = 0.008). The APEX1 148Glu allele was also associated with increased lung cancer risk among male smokers, especially among heavy smokers in both case-control studies (odd ratio: 4.40, 95%CI: 3.29-5.72). In addition, APEX1 148Glu variant interacts with smoking in increasing male lung cancer risk, as measured by the attributable proportion due to interaction, which was 0.23 (95%CI: 0.06-0.39). This study showed evidence on interaction between APEX1 148Glu variant and cigarette smoking in increasing lung cancer susceptibility among male Chinese, which may be due to the synergistic effects of APEX1 148Glu and PAHs in increasing chromosome damage levels. The results provide a new insight into gene-interactions in lung carcinogenesis.
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Oncology, the Second Hospital of Wuhan Iron and Steel (Group) Corporation, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Oncology, the Second Hospital of Wuhan Iron and Steel (Group) Corporation, Wuhan, China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Die
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Meian
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D016022:Case-Control Studies; D002681:China; D002869:Chromosome Aberrations; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000235:genetics; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*
chemical_list: D000395:Air Pollutants, Occupational; D011084:Polycyclic Aromatic Hydrocarbons; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: DNA damage; apurinic/apyrimidinic endonuclease 1; cigarette smoking; gene-environment interaction; lung cancer; micronucleus frequency; polycyclic aromatic hydrocarbons