Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI (< or = 5), CAE > 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48; 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04; 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women.

To examine the association between ingested inorganic arsenic and prevalence of diabetes mellitus, in 1988, the authors studied 891 adults residing in villages in southern Taiwan where arseniasis is hyperendemic. The status of diabetes mellitus was determined by an oral glucose tolerance test and a history of diabetes regularly treated with sulfonylurea or insulin. The cumulative arsenic exposure in parts per million-years was calculated from the detailed history of residential addresses and duration of drinking artesian well water obtained through standardized interviews based on a structured questionnaire and the arsenic concentration in well water. The body mass index was derived from body height and weight measured according to a standard protocol, while the physical activity at work was also obtained by questionnaire interviews. Residents in villages where the chronic arseniasis was hyperendemic had a twofold increase in age- and sex-adjusted prevalence of diabetes mellitus compared with residents in Taipei City and the Taiwan area. There was a dose-response relation between cumulative arsenic exposure and prevalence of diabetes mellitus. The relation remained significant after adjustment for age, sex, body mass index, and activity level at work by a multiple logistic regression analysis giving a multivariate-adjusted odds ratio of 6.61 and 10.05, respectively, for those who had a cumulative arsenic exposure of 0.1-15.0 and greater than 15.0 ppm-year compared with those who were unexposed. These results suggest the chronic arsenic exposure may induce diabetes mellitus in humans.

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To examine the association between long-term exposure to inorganic arsenic and the prevalence of hypertension, we studied a total of 382 men and 516 women residing in villages where arseniasis was hyperendemic. Hypertension was defined as a systolic blood pressure of 160 mm Hg or greater, a diastolic blood pressure of 95 mm Hg or greater, or a history of hypertension treated regularly with antihypertensive drugs. The long-term arsenic exposure was calculated from the history of artesian well water consumption obtained through standardized interviews based on a structured questionnaire and the measured arsenic concentration in well water. Residents in villages where long-term arseniasis was hyperendemic had a 1.5-fold increase in age- and sex-adjusted prevalence of hypertension compared with residents in nonendemic areas. Duration of artesian well water consumption, average arsenic concentration in drinking water, and cumulative arsenic exposure were all significantly associated with hypertension prevalence. The higher the cumulative arsenic exposure, the higher the prevalence of hypertension. This dose-response relation remained significant after adjustment for age, sex, diabetes mellitus, proteinuria, body mass index, and serum triglyceride level. The results suggest that long-term arsenic exposure may induce hypertension in humans.

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Background-Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. This study further examined the biological gradient between ingested inorganic arsenic and carotid atherosclerosis. Methods and Results-We studied 199 male and 264 female adult residents from the southwestern area of endemic arseniasis in Taiwan. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Diabetes mellitus was determined by oral glucose tolerance test, hypertension by mercury sphygmomanometers, and serum lipid profiles by autoanalyzers. Information regarding the consumption of high-arsenic artesian well water, cigarette smoking, and alcohol consumption was obtained through standardized questionnaire interviews. Logistic regression analysis was used to estimate the odds ratio and its 95% CI of carotid atherosclerosis for various risk factors. Three indices of long-term exposure to ingested arsenic, including the duration of consuming artesian well water, the average arsenic concentration in consumed artesian well water, and cumulative arsenic exposure, were all significantly associated with prevalence of carotid atherosclerosis in a dose-response relationship. The biological gradient remained significant after adjustment for age, sex, hypertension, diabetes mellitus, cigarette smoking, alcohol consumption, waist-to-hip ratio, and serum levels of total cholesterol and LDL cholesterol. The multivariate-adjusted odds ratio was 3.1 (95% CI 1.3 to 7.4) for those who had a cumulative arsenic exposure of Ն20 mg/L-years compared with those without exposure to arsenic from drinking artesian well water. Conclusions-Carotid atherosclerosis is associated with ingested inorganic arsenic, showing a significant biological

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