The aim is to assess dose-response association between arsenic exposure,DNA damage biomark-ers,and the incidence of bladder and kidney cancers.A total of 8102 men and women from 3901 households have been enrolled in 1991-1994,and followed in 2011-2014.The data collected included well water consumption,habits of cigarette smoking,alcohol consumption,exercise and diet,through standardized personal interview.The individual urinary arsenic species were quantified using high-performance liquid chromatography-inductively coupled plasma/mass spectrometry (HPLC-ICP/MS).For assessment of oxidative and methylated DNA lesions and depletion,urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and N7-methylguanine (N7-MeG) were measured respectively,using liquid chromatography/tandem mass spectrometry (LC-MS/MS).The National Cancer Registry Data using the pathology finding defined bladder and kidney cancers.Urinary levels of the two DNA adduct increased significantly with increasing urinary arsenic level (iAs+MMA+DMA) in both men (β=0.82,β = 0.34 for 8-oxodG and N7-MeG,respectively,p < 0.0001 for both) and women (β = 1.03,0.38,p<0.0001) adjusted for potential confounders.Incidence rate of bladder and kidney cancer using person-years tended to be the highest for higher urinary inorganic and methylated arsenic with higher DNA adduct level than the medians.It is suggested that subjects with high arsenic exposure experienced further cancer risk with high level of DNA damage biomarker.
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