Hsu KH, Tsui KH, Hsu LI, Chiou HY, Chen CJ. Dose-Response Relationship between Inorganic Arsenic Exposure and Lung Cancer among Arseniasis Residents with Low Methylation Capacity. Cancer Epidemiol Biomarkers Prev. 2016 Dec 22. pii: cebp.0281.2016. doi: 10.1158/1055-9965.EPI-16-0281.
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 1300 residents from an arseniasis area in Taiwan, determined urinary InAs metabolites, and identified 39 lung cancer cases. Cox proportional hazard model was performed.
Results: The results demonstrated that participants with either the primary methylation index (monomethylarsonic acid [MMA]/InAs) or the secondary methylation index (dimethylarsinic acid[DMA]/MMA) lower than their respective median values were at a higher risk of lung cancer (hazard ratios from 3.41 to 4.66) than those with high methylation capacity. The incidence density of lung cancer increased from 79.9/100000 (year-1) to 467.4/100000 (year-1) for residents with low methylation capacity and from 0 to 158.5/100000 (year-1) for residents with high methylation capacity when the arsenic exposure dose increased from 2-10 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 < .05 and P < .05, respectively) among the residents with low methylation capacity. The relationship between arsenic exposure and lung cancer among high methylaters 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.