Association between arsenic exposure, DNA damage, and urological cancers incidence: A long-term follow-up study of residents in an arseniasis endemic area of northeastern Taiwan

[[abstract]]Arsenic is a well-established human carcinogen and is considered a health risk worldwide, especially where groundwater is consumed as drinking water. In 2018, bladder and kidney cancers were the 14th and 17th leading causes of global cancer mortality, respectively. Our aim was to investigate the association between arsenic exposure, DNA damage, and the incidence of bladder and kidney cancers. A total of 788 participants aged ≥40 years were enrolled in a prospective cohort study in Taiwan between 1991 and 1994, with follow-up between 2011 and 2014. Well-water and first-morning spot urine samples were collected between 1991 and 1994 to estimate arsenic exposure, and the baseline urinary levels of 8-Oxo-2′-deoxyguanosine (8-OHdG) and N7-methylguanine (N7-MeG) were quantified to assess DNA lesions. The Cox proportional hazard model was used to estimate the effects of arsenic exposure and DNA adduct levels on the risk of bladder or kidney cancer. Urinary arsenic species were associated with significantly increased 8-OHdG and N7-MeG after adjusting for age, sex, and cigarette smoking. Only non-statistically significant mediation effects of 8-OHdG were observed. In a fully adjusted Cox model, participants with arsenic exposure and urinary 8-OHdG levels higher than the median had a higher risk of bladder cancer (HR = 4.60, confidence interval: 1.43–14.85). Overall, the combined effects of high cumulative arsenic exposure from artesian well-water and advanced DNA damage predicted the risk of bladder cancer