title: Personal exposure to PM2.5, genetic variants and DNA damage: a multi-center population-based study in Chinese.
abstract: Exposure to particulate matter (e.g., PM2.5) may result in DNA damage, a major culprit in mutagenesis and environmental toxicity. DNA damage levels may vary among individuals simultaneously exposed to PM2.5, however, the genetic determinants are still unclear. To explore whether PM2.5 exposure and genetic variants contribute to the alteration in DNA damage, we recruited 328 subjects from three independent cohorts (119 from Zhuhai, 123 from Wuhan and 86 from Tianjin) in southern, central and northern China with different PM2.5 exposure levels. Personal 24-h PM2.5 exposure levels and DNA damage levels of peripheral blood lymphocytes were evaluated. Genotyping were performed using Illumina Human Exome BeadChip with 241,305 single nucleotide variants (SNVs). The DNA damage levels are consistent with the PM2.5 exposure levels of each cohort. A total of 35 SNVs were consistently associated with DNA damage levels among the three cohorts with pooled P values less than 1.00×10(-3) after adjustment for age, gender, smoking status and PM2.5 exposure levels, of which, 18 SNVs together with gender and PM2.5 exposure levels were independent factors contributing to DNA damage. Gene-based test revealed 3 genes significantly associated with DNA damage levels (P=5.11×10(-3) for POLH, P=2.88×10(-3) for RIT2 and P=2.29×10(-2) for CNTN4). Gene ontology (GO) analyses indicated that the identified variants were significantly enriched in DNA damage response pathway. Our findings highlight the importance of genetic variation as well as personal PM2.5 exposure in modulating individual DNA damage levels.
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Epidemiology and Biostatistics, School of Public Health, Nantong University, Nantong, Jiangsu, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Chongqi
authors.initials: C
authors.lastname: Sun
authors.affiliation: Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jianhang
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Mulong
authors.initials: M
authors.lastname: Du
authors.affiliation: Key Laboratory of Modern Toxicology of Ministry of Education, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Kan
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: hbshen@njmu.edu.cn.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China; D004249:DNA Damage; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*
chemical_list: D052638:Particulate Matter
keywords: Comet assay; DNA damage; Genetic variants; PM2.5 exposure; Population-based study