Superfund Research Program
Arsenic and Health in Taiwan and Bangladesh
Project Leader: David C. Christiani
Grant Number: P42ES005947
Funding Period: 2000 - 2006
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Final Progress Reports
Year: 2005
The aims of this project are to assess the role of drinking water arsenic in the risk of skin lesions, including cancerous and precancerous lesions, such as hyperkeratosis, hypermelanosis and hypopigmentation. A case-control design, with a total of 1,600 participants has been completed, with complete clinical and laboratory data on 1,200.
Dr. Christiani’s laboratory investigated the reliability of toenail arsenic as an exposure marker to predict disease in 600 cases and 600 controls loosely matched on age and gender in community clinics in Pabna, Bangladesh in 2001-2002. On the common log scale, one unit increase in water arsenic concentration corresponds to a 1.92 (95%CI 1.83-2.02) fold increase in nail arsenic concentration. Results were similar for analysis restricted to controls (1.85 95% CI 1.72-1.99). Odds of skin lesions increased 14% (OR=1.14; 95%CI 1.10-1.17) per 50µgAs/l increase and almost 3 fold (OR=2.80; 95% CI 2.17-3.63) increase per 10-fold increase in nail arsenic. GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status, whether water (OR1.56; 95% CI 1.10-2.19) or nail arsenic (OR1.59; 95%CI 1.13-2.23) concentration was modeled. The GSTP1 GG polymorphism was associated with a greater odds of skin lesions compared to GSTP1 AA, whether drinking water arsenic concentration (OR 1.86; 95%CI 1.15-3.00), or toenail arsenic concentration (OR 1.89; 95%CI 1.18-3.04)) was modeled. Skin lesions can be predicted reliably using toenail or water arsenic concentration. Disease status does not impact toenail arsenic concentration. Effect modification of GSTT1, GSTM1 and GSTP1 polymorphisms on skin lesions or arsenic concentration of toenails was not detected.
In a companion study of healthy individuals using a repeated measures design, Dr. Christiani’s group assessed exposure and genetic markers. Toenail arsenic concentrations were evaluated as a biomarker of inorganic arsenic exposure in a population residing in an arsenic-endemic region of Bangladesh. Drinking water and toenail samples were collected from 48 families (N=223) every three months for two years and analyzed for arsenic using inductively coupled plasma-mass spectrometry. Drinking water collected three, six, and nine months prior to each toenail sample was combined into a weighted lagged exposure variable. The best model attributed 69%, 14%, and 17% of the toenail arsenic content to drinking water exposures that occurred three, six, and nine months prior to toenail collection, respectively. Below a drinking water concentration of 2 µg As/L, no relationship between drinking water arsenic and toenail arsenic concentrations was observed. Above this concentration, toenail arsenic content increased in a dose dependent fashion as drinking water arsenic increased. Age was a significant effect modifier of drinking water arsenic exposure on toenail arsenic (β = 0.01, 95% C.I. 0.0015– 0.02). Individuals possessing GSTT1 null [GSTT1(-)] genotypes had significantly more arsenic in their toenails in contrast to GSTT1 wildtype individuals (β = 0.11, 95% C.I. 0.064– 0.2). Therefore, it appears that GSTT1 modifies the relationship between Asin exposure and toenail Asin content.
Dr. Christiani’s group also investigated the impact of diet and betel nut use on skin lesions associated with drinking water arsenic in Pabna, Bangladesh. In 450 cases and 450 controls loosely matched on age and gender. Diet, demographic data and water samples were collected. Water samples were analyzed for arsenic using Inductively Coupled Plasma Mass Spectroscopy (ICP-MS).
Interestingly, betel nut use was associated with a greater risk of skin lesions in a multivariate model (OR 1.67; 95% CI= 1.18-2.36). Bean intake at least 1 time/day (OR 1.89; 95%CI 1.11-3.22) was associated with an increased risk of skin lesions. Modest decreases in risk of skin lesions were associated with fruit intake 1-3 times/month (OR 0.68; 95%CI 0.51-0.89), and canned goods at least 1 time/month (OR 0.41; 95%CI 0.20-0.86). Increased fruit and intake of canned goods may be associated with reduced risk of lesions. Increased intake of beans may be associated with an increased risk of skin lesions. The results of this study do not provide clear support for a protective effect of vegetable and overall protein consumption against the development of skin lesions, but a modest benefit cannot be excluded.