title: Dose-Response Relationship between Inorganic Arsenic Exposure and Lung Cancer among Arseniasis Residents with Low Methylation Capacity.
abstract: Background:Exposure to inorganic arsenic (InAs) has been documented as a risk factor for lung cancer. This study examined the association between InAs exposure, its metabolism, and lung cancer occurrence.Methods:We followed 1,300 residents from an arseniasis area in Taiwan, determined urinary InAs metabolites, and identified 39 lung cancer cases. Cox proportional hazards model was performed.Results:The results demonstrated that participants with either the primary methylation index [monomethylarsonic acid (MMA)/InAs] or the secondary methylation index [dimethylarsenic acid (DMA)/MMA] lower than their respective median values were at a higher risk of lung cancer (HRs from 3.41 to 4.66) than those with high methylation capacity. The incidence density of lung cancer increased from 79.9/100,000 (year-1) to 467.4/100,000 (year-1) for residents with low methylation capacity and from 0 to 158.5/100,000 (year-1) for residents with high methylation capacity when the arsenic exposure dose increased from 2 to 10 ppb to ≥200 ppb, respectively. The analyses revealed a dose-response relationship between lung cancer occurrence and increasing arsenic concentrations in drinking water as well as cumulative arsenic exposure (monotonic trend test;P< 0.05 andP< 0.05, respectively) among the residents with low methylation capacity. The relationship between arsenic exposure and lung cancer among high methylators was not statistically significant.Conclusions:Hypomethylation responses to InAs exposure may dose dependently increase lung cancer occurrence.Impact:The high-risk characteristics observed among those exposed should be considered in future preventive medicine and research on arsenic carcinogenesis.Cancer Epidemiol Biomarkers Prev; 26(5); 756-61. ©2016 AACR.
authors.affiliation: Laboratory for Epidemiology, Department of Health Care Management and Healthy Aging Research Center, Chang Gung University, Taoyuan City, Taiwan.|Department of Urology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
authors.forename: Kuang-Hung
authors.initials: KH
authors.lastname: Hsu
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
authors.forename: Ke-Hung
authors.initials: KH
authors.lastname: Tsui
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei City, Taiwan. hychiou@tmu.edu.tw chencj@gate.sinica.edu.tw.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan. hychiou@tmu.edu.tw chencj@gate.sinica.edu.tw.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001151:Arsenic / Q000378:metabolism*; D020261:Arsenic Poisoning / Q000150:complications* / Q000453:epidemiology; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000378:metabolism; D008297:Male; D008745:Methylation; D008875:Middle Aged; D012307:Risk Factors; D013624:Taiwan; D014874:Water Pollutants, Chemical / Q000506:poisoning
chemical_list: D014874:Water Pollutants, Chemical; D001151:Arsenic