Volume 24 Issue 8 - August 30, 2013 PDF
Arsenic levels in drinking water and mortality of liver cancer in Taiwan
Tzu-I Sunga, Hung-Jung Linb, Chi-Yi Chenc, How-Ran Guo,d*
aDepartment of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
bCancer Research Center and Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan
cDepartment of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
dDepartment of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
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The carcinogenic effect of arsenic has been documented for more than a century,[1] and the World Health Organization (WHO) proposed a quality guideline of 0.01 mg/L for inorganic arsenic in drinking water in 1993. Whereas a positive dose-response relationship between arsenic levels and mortality of liver cancer in men (but not in women) was reported in Taiwan originally,[3] no particular strong dose-response relationship was observed when Morales et al.[4] Therefore, we conducted a study in 138 villages in the southwest coast area of Taiwan to evaluate the dose-response relationship between arsenic in drinking water and mortality of liver cancer.

The model
We reviewed death certificates from 1971 to 1990 to identify liver cancer cases and assessed arsenic levels in drinking water using data from a survey conducted by the government. According to the standard solutions used in the survey[5] and results from previous studies,[6] arsenic levels can be grouped into six categories: below 0.05 mg/L, 0.05-0.08 mg/L, 0.09-0.16 mg/L, 0.17-0.32 mg/L, 0.33-0.64 mg/L, and above 0.64 mg/L. Using village as the unit, we conducted multi-variate regression analyses using the following model:
R = α + β1X1 +...+ β5X5 + γ1A1 +...+ γ3A3
[Model 1],

where for each village, R is the mortality of liver cancer, Xj is proportion (expressed as percentage) of wells with arsenic concentrations in category j, and Ap is proportion of residents in age group p. In this case, α (intercept) is the estimated background risk, and βj indicates the RD associated with each 1% increase in wells in category j. Furthermore, the data were weighted with the total population in each village as the weight, and weighted regression models were applied to account for the different weights of data contributed by different villages.

Dose-response relationship
During the 20-year period, 802 male and 301 female mortality cases of liver cancer were identified. After adjusting for age, arsenic levels above 0.64 mg/L were associated with an increase in the liver cancer mortality in both genders, but no significant effect was observed for lower exposure categories. (Table 1)

Table 1. Estimates of rates difference (per 100,000 persons-year) by gender.

aconfidence interval; *p < 0.05

Post-hoc analyses
As shown by Model 1, there was a significant positive effect above 0.64 mg/L but no significant effecte below 0.64 mg/L. Accordingly, two post-hoc multiple regression models were applied to validate the observations. One with all exposure between 0.05 and 0.64 mg/L being combined as one predictor variable, X14 , as the following:
R = α1 + β14X14 + β5X5 + γ1A1 +...+ γ3A3
[Model 2],

and the results showed that this new variable (X14) was not a predictor of the mortality of liver cancer. This model is to examine whether there is a significant effect of levels between 0.05 and 0.64 mg/L. The other model had only one indicator for arsenic exposure—for levels above 0.64 mg/L, assuming no significant effect of arsenic in drinking water below 0.64 mg/L as the following:
R = α2 + β5X5 + γ1A1 +...+ γ3A3
[Model 3],

Both Models 2 and 3 generated similar point estimates for the increases in liver cancer mortality associated with arsenic levels above 0.64 mg/L as the full model.

Furthermore, we validated the observed dose-response relationships further by dividing the 138 villages into the following three groups: the Group A consisted of 29 villages with all wells containing less than 0.05 mg/L of arsenic, Group B consisted of 74 villages with some wells containing more than 0.05 mg/L of arsenic but none with arsenic levels above 0.64 mg/L, and Group C consisted of 35 villages with some wells containing more than 0.64 mg/L of arsenic. If conclusions drawn on the dose-response relationship from regression analyses hold, Group C should have the highest mortality among the three, and Groups A and B should have similar mortality rates. The first projection was true in all but two groups—men below 29 years of age and women between 50 and 69 years old, and the difference between Group C and the group with the highest mortality were not statistically significant in either case (Table 2). The second projection was supported by the facts that both Group A and Group B had higher liver cancer mortality in four of the eight gender-age groups and that all the differences between Groups A and B were not statistically significant except for women between 50 and 69 years old. Therefore, results of stratified analyses confirmed the dose-response relationships projected by the regression analyses.

Table 2. Post-Hoc stratified analyses for comparison of liver cancer mortality (per 100,000 person-year) among Group A (all [As] < 0.05 mg/L), Group B (some [As] > 0.05 mg/L, but none > 0.64 mg/L), and Group C (some [As] > 0.64 mg/L).

*p < 0.05; ** p < 0.01

We concluded that exposures to high arsenic levels in drinking water are associated with the occurrence of liver cancer, but such an effect is not prominent at low exposure levels. The quality guideline set by the World Health Organization for arsenic in drinking water may provide sufficient protection.

  1. Hutchinson J. Arsenic cancer. Br Med J 188;72: 1280-1281.
  2. World Health Organization. WHO Guidelines for Drinking Water Quality, Volume 1. Geneva, Switzerland: World Health Organization, 1993.
  3. Wu M-M, Kuo T-L, Hwang Y-H, Chen C-J. Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. Am J Epidemiol 1989;120: 1123-1132.
  4. Morales KH, Ryan L, Kuo T-L, Wu M-M, Chen C-J. Risk of internal cancers from arsenic in drinking water. Environ Health Perspect 2000;108: 655-661.
  5. Lo M-C, Hsen Y-C, Lin B-K. Second Report on the Investigation of Arsenic Content in Underground Water in Taiwan. Taichung, Taiwan: Taiwan Provincial Institute of Environmental Sanitation, 1977.
  6. Guo H-R, Chiang H-S, Hu H, Lipsitz SR, Monson RR. Arsenic in drinking water and incidence of urinary cancers. Epidemiology 1997;8: 545-550.
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