Hsueh Y M, Chiou H Y, Huang Y L, Wu W L, Huang C C, Yang M H, Lue L C, Chen G S, Chen C J
First Department of Public Health, School of Medicine, Taipei Medical College, Taiwan.
Cancer Epidemiol Biomarkers Prev. 1997 Aug;6(8):589-96.
To elucidate the associations of arsenic-induced skin cancer with serum beta-carotene level and arsenic methylation capability, a total of 654 residents of age 30 or older were recruited from three arseniasis-hyperendemic villages in Taiwan and regularly examined for skin lesions during the follow-up period. There were 33 cases affected with newly diagnosed skin cancer during the follow-up, giving an incidence of 14.74 per 1000 person-years. Although most study subjects had stopped consuming high-arsenic artesian well water more than 20 years ago, the risk of skin cancer was found to increase significantly with cumulative arsenic exposure before the cessation of drinking artesian well water in a dose-response relationship. Frozen serum samples collected at the recruitment from newly developed skin cancer cases and matched controls were tested for beta-carotene levels by high-performance liquid chromatography. Frozen urine samples of these subjects were examined by high-performance liquid chromatography to speciate arsenite (AsIII), arsenate (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 methylation capability indexed by the ratio of MMA/(AsIII + AsV) was greater in cases than in controls, the secondary methylation capability indexed by the ratio of dimethylarsinic acid/MMA was lower in cases than 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 > or = 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 as high as 20.91 (95% confidence interval, 2.63-166.5) compared wih those who had a cumulative arsenic exposure of <20.0 mg/liter-year and a MMA percentage of < or = 26.7%. Whether the association with capability of inorganic methylation is also applied to cancers of internal organs, including lung, liver, and urinary bladder, remains to be elucidated.
为阐明砷所致皮肤癌与血清β-胡萝卜素水平及砷甲基化能力之间的关联，从台湾三个砷中毒高流行村庄招募了654名30岁及以上居民，并在随访期间定期检查皮肤病变情况。随访期间有33例新诊断为皮肤癌，发病率为每1000人年14.74例。尽管大多数研究对象在20多年前就已停止饮用高砷自流井水，但发现皮肤癌风险随停止饮用自流井水前的累积砷暴露量呈剂量反应关系显著增加。对新患皮肤癌病例及匹配对照在招募时采集的冷冻血清样本，采用高效液相色谱法检测β-胡萝卜素水平。通过高效液相色谱法对这些受试者的冷冻尿液样本进行检测，以确定亚砷酸盐（AsIII）、砷酸盐（AsV）、一甲基胂酸（MMA）和二甲基胂酸，然后采用氢化物发生器结合原子吸收光谱法进行定量。皮肤癌病例的血清β-胡萝卜素水平显著低于匹配的健康对照。尽管以MMA/(AsIII + AsV)比值为指标的初级甲基化能力病例高于对照，但以二甲基胂酸/MMA比值为指标的次级甲基化能力病例低于对照。尿总砷水平中MMA比例升高与皮肤癌风险增加相关。累积砷暴露量≥20.0毫克/升·年且尿总砷水平中MMA比例>26.7%的受试者，与累积砷暴露量<20.0毫克/升·年且MMA百分比≤26.7%的受试者相比，发生皮肤癌的多因素调整优势比高达20.91（95%置信区间，2.63 - 166.5）。与无机甲基化能力的关联是否也适用于包括肺、肝和膀胱在内的内脏器官癌症，仍有待阐明。
