SERUM BETA-CAROTENE LEVEL, ARSENIC METHYLATION CAPABILITY, AND INCIDENCE OF SKIN-CANCER

To elucidate the associations of arsenic-induced skin cancer with seru m p-carotene level and arsenic methylation capability, a total of 654 residents of age 30 or older were recruited from three arseniasis-hype rendemic villages in Taiwan and regularly examined for skin lesions du ring the follow-up period. There were 33 cases affected with newly dia gnosed skin cancer during the follow-up, giving an incidence of 14.74 per 1000 person-years. Although most study subjects had stopped consum ing high-arsenic artesian well water more than 20 years ago, the risk of skin cancer was found to increase significantly with cumulative ars enic exposure before the cessation of drinking artesian well water in a dose-response relationship. Frozen serum samples collected at the re cruitment from newly developed skin cancer cases and matched controls were tested for beta-carotene levels by high-performance liquid chroma tography. Frozen urine samples of these subjects were examined by high -performance liquid chromatography to speciate arsenite (AsIII), arsen ate (AsV), monomethylarsonic acid (MMA), and dimethylarsinic acid and then quantitated by hydride generator combined with atomic absorption spectrometry. Skin cancer cases had a significantly lower serum level of beta-carotene than matched healthy controls. Although the primary m ethylation capability indexed by the ratio of MMA/(AsIII + AsV) was gr eater in cases than in controls, the secondary methylation capability indexed by the ratio of dimethylarsinic acid/MMA was lower in cases th an in controls. An elevated proportion of MMA in total urinary arsenic level was associated with an increased risk of skin cancer. Subjects with a cumulative arsenic exposure of greater than or equal to 20.0 mg /liter-year and a proportion of MMA in total urinary arsenic level >26 .7% had a multivariate-adjusted odds ratio of developing skin cancer a s high as 20.91 (95% confidence interval, 2.63-166.5) compared with th ose who had a cumulative arsenic exposure of <20.0 mg/liter-year and a MMA percentage of less than or equal to 2 6.7%. Whether the associati on with capability of inorganic methylation is also applied to cancers of internal organs, including lung, liver, and urinary bladder, remai ns to be elucidated.