Chen Yen-Ching, Su Huey-Jen Jenny, Guo Yu-Liang Leon, Hsueh Yu-Mei, Smith Thomas J, Ryan Louise M, Lee Meei-Shyuan, Christiani David C
Occupational Health Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Cancer Causes Control. 2003 May;14(4):303-10. doi: 10.1023/a:1023905900171.
The mechanism of arsenic detoxification in humans remains unclear. Data are especially lacking for low-level arsenic exposure. We hypothesize that arsenic methylation ability, defined as the ratios of monomethylarsonic acid (MMA(V))/inorganic arsenic (primary arsenic methylation index, PMI) and dimethylarsinic acid (DMA(V))/ MMA(V) (secondary arsenic methylation index, SMI), may modify the association between cumulative arsenic exposure (CAE, mg/L-year) and the risk of bladder cancer. In this study we investigated the relationship among arsenic methylation ability, CAE, and the risk of bladder cancer in a hospital-based case-control study in southwestern Taiwan.
From January 1996 to December 1999 we identified 49 patients with newly diagnosed cases of bladder cancer at the National Cheng-Kung University (NCKU) Medical Center; controls consisted of 224 fracture and cataract patients selected from the same medical center. The levels of four urinary arsenic species: arsenite (As(III)), arsenate (As(V)), MMA(V), and DMA(V)) were determined in all subjects by using the high-performance liquid chromatography hydride-generation atomic absorption spectrometry (HPLC-HGAAS). CAE was estimated by using published data collected in a survey from 1974 to 1976.
Compared to a CAE < or = 2 mg/L-year, CAE > 12 mg/L-year was associated with an increased risk of bladder cancer (multivariate odds ratio (OR) 4.23, 95% confidence interval (CI) 1.12-16.01), in the setting of a low SMI (< or = 4.8). Compared to women, smoking men (OR 6.23, 95% CI 1.88-20.62) and non-smoking men (OR 3.25, 95% CI 0.95-11.06) had higher risks of bladder cancer. Given the same level of PMI, smoking men (OR 9.80, 95% CI 2.40-40.10) and non-smoking men (OR 4.45, 95% CI 1.00-19.84) had a higher risk of bladder cancer when compared to women. With the same level of SMI, both smoking men (OR 6.28, 95% CI 1.76-22.39) and non-smoking men (OR 3.31, 95% CI 0.84-12.97) had a higher risk of bladder cancer when compared to women.
Subjects with low SMI have a substantially increased risk of bladder cancer, especially when combined with high CAE levels.
人体中砷解毒的机制仍不清楚。对于低水平砷暴露的数据尤其缺乏。我们假设砷甲基化能力，定义为一甲基胂酸（MMA(V)）/无机砷（初级砷甲基化指数，PMI）和二甲基胂酸（DMA(V)）/MMA(V)（次级砷甲基化指数，SMI）的比值，可能会改变累积砷暴露（CAE，mg/L - 年）与膀胱癌风险之间的关联。在本研究中，我们在台湾西南部一项基于医院的病例对照研究中，调查了砷甲基化能力、CAE与膀胱癌风险之间的关系。
从1996年1月至1999年12月，我们在国立成功大学医学中心确定了49例新诊断的膀胱癌患者；对照组由从同一医学中心选取的224例骨折和白内障患者组成。通过使用高效液相色谱 - 氢化物发生原子吸收光谱法（HPLC - HGAAS）测定所有受试者尿液中四种砷形态：亚砷酸盐（As(III)）、砷酸盐（As(V)）、MMA(V)和DMA(V)）的水平。CAE通过使用1974年至1976年一项调查中收集的已发表数据进行估算。
与CAE≤2 mg/L - 年相比，在低SMI（≤4.8）的情况下，CAE>12 mg/L - 年与膀胱癌风险增加相关（多变量优势比（OR）4.23，95%置信区间（CI）1.12 - 16.01）。与女性相比，吸烟男性（OR 6.23，95% CI 1.88 - 20.62）和不吸烟男性（OR 3.25，95% CI 0.95 - 11.06）患膀胱癌的风险更高。在PMI水平相同的情况下，与女性相比，吸烟男性（OR 9.80，95% CI 2.40 - 40.10）和不吸烟男性（OR 4.45，95% CI 1.00 - 19.84）患膀胱癌的风险更高。在SMI水平相同的情况下，与女性相比，吸烟男性（OR 6.28，95% CI 1.76 - 22.39）和不吸烟男性（OR 3.31，95% CI 0.84 - 12.97）患膀胱癌的风险更高。
SMI低的受试者患膀胱癌的风险大幅增加，尤其是在与高CAE水平相结合时。
