3.1. Arsenic concentration in the Hamadan province
According to the results, the average concentration of As in Kaboodarahang, Nahavand, and Malayer was higher than the recommended limit offered by WHO. In Table 1 the summary of the results of the As concentration during five years was presented, including the mean, std. deviation, Kurtosis and Skewness. In rural regions of Kaboodarahang, including Qapaqtapeh-ye Kord, Churmaq, Quhurd-e Olya, Qohurd-e Sofla, Jaganlu, the concentration of arsenic in groundwater were obtained 91.73 ± 19.81, 100.45 ± 20.3, 185.4 ± 69.05, 180.5 ± 31.2, 160.75 ± 41.64, respectively. In some areas of Malayer and Nahavand, the As concentration ranged 1.7–10 times higher than standard values. The spatial modeling showed the highest concentration of arsenic in Kaboodarahang county. The arsenic sources in this region were related to specific geological conditions, volcanic rocks, and sulfide compounds (Malakootian & Khashi, 2014; Mosaferi et al., 2017). The most of the natural arsenic contamination in Iran has occurred along the belt of Tertiary volcanic rocks stretches from Turkey to Pakistan(Hamidian et al., 2019). In a study by Barzegar in East Azarbaijan (the northwest of Iran), the mean concentration of arsenic in groundwater was obtained 150 ppb (Barzegar et al., 2015).
Table 1
The summary of statistics for measured concentrations of arsenic in the water samples collected from 9 counties of Hamadan
Counties
|
Min
|
Max
|
Mean
|
Std. Deviation
|
Skewness
|
Kurtosis
|
Statistic
|
Std. Error
|
Statistic
|
Std. Error
|
kaboodarahang
|
.00
|
185.40
|
40.1
|
50.72
|
1.83
|
0.37
|
2.52
|
0.74
|
Tuyserkan
|
.00
|
1.67
|
0.28
|
.600
|
1.98
|
0.63
|
2.51
|
1.23
|
Razan
|
.00
|
.65
|
0.14
|
.260
|
1.47
|
0.63
|
.390
|
1.23
|
Nahavand
|
.00
|
29.81
|
6.1
|
10.32
|
1.77
|
0.61
|
1.97
|
1.19
|
Malayer
|
.00
|
102.80
|
13.10
|
30.057
|
2.55
|
0.58
|
5.99
|
1.12
|
Hamadan
|
.00
|
0.00
|
0.00
|
.000
|
.
|
.
|
.
|
.
|
Famenin
|
.00
|
1.41
|
0.36
|
0.59
|
1.37
|
0.75
|
.050
|
1.48
|
Bahar
|
.00
|
12.25
|
2.05
|
3.64
|
1.94
|
0.58
|
3.47
|
1.12
|
Asadabad
|
.00
|
1.60
|
0.36
|
.57
|
1.65
|
0.71
|
1.97
|
1.40
|
In Kaboodarahang, where arsenic pollution is higher than in other places in Hamadan province, The bottom layer of the earth's crust consists of slate/phyllite rocks, which, among the various rocks (such as peaty soils and mud stones/marine shales) has the maximum concentration of arsenic(Shaji et al., 2021). In the Hamadan province, like other areas with arid and semiarid climates, to access more water resources, wells are drilled into deeper rocks which affects water quality in terms of arsenic pollution. Based on the past works, there is a significant positive relationship between well depth and arsenic concentration (Barzegar et al., 2015; Li et al., 2018). In a study by Li, the maximum concentration of arsenic was found in the depth of 25 meters, and the estimated target cancer risk values at the depths 25 m ranged from 1.32 ×10− 4 to 5.87×10− 2, while at a depth of 10 m were obtained as 3.86 × 10− 4 − 1.04 × 10− 4 (Li et al., 2018). In another study by Barzegar, the As concentration was measured in water samples from deep and shallow wells (8-150 m depth), and the highest concentration was obtained from a depth of 120 m(Barzegar et al., 2015).
3.2. Correlation Of As Concentration And Bladder Cancer And Leukemia Mortality
The effect of arsenic concentration on the mortality rate of urological and blood cancer at a 95% confidence interval was shown in Table 2. According to this study, arsenic exposure was significantly associated with the mortality rate of urological cancer (p = 0.042). Based on linear regression fitting, for each unit increase in arsenic concentration in groundwater, the mortality rate from this cancer increases by an average of 0.13. The data are scattered around a straight line with a positive slope and the rate of increase is statistically significant (Fig. 4).
Table 2
The summary of results of regression analysis
|
parameters
|
coefficient
|
Std.Error
|
Standardized Coefficients
|
t
|
P_value
|
Urological cancer
|
constant
|
1.8
|
0.69
|
|
2.58
|
0.036
|
|
Arsenic
|
0.13
|
0.05
|
0.69
|
2.48
|
0.042
|
|
|
R2 = 0.47
|
F = 6.19
|
P_value = 0.042
|
|
|
leukemia
|
constant
|
3.75
|
0.91
|
|
4.08
|
0.005
|
|
Arsenic
|
0.34
|
0.13
|
0.71
|
2.65
|
0.033
|
|
|
R2 = 0.50
|
F = 7.02
|
P_value = 0.033
|
|
|
In a previous ecological study in Chile, the association between arsenic in drinking water and mortality rate due to bladder cancer has been evaluated using Poisson regression. According to the results, in agreement with the current study, an increase in the rate of bladder cancer mortality was found in Chile, even 40 years after high arsenic exposure. Arsenic levels of drinking water in the study areas in Chile decreased from 600 to 20 micrograms during the 1960s and 2010. In spite of that, the adverse effects of arsenic have been observed up to four decades after arsenic depletion(Smith et al., 2018).
In accordance with the present study, in most previous studies, exposure to high levels of arsenic was significantly associated with mortality rate of bladder cancer. For example, the results of a review study of 30 years of ecologic evidences by Saint-Jacques et al., supported a strong association between high levels of arsenic in drinking water and the risk of death from bladder cancer. However, due to the limitations of epidemiological studies, the threshold level for exposure to arsenic in drinking water without causing health effects has not yet been determined (Saint-Jacques et al., 2014).
Some previous studies, have shown a weak association between low arsenic concentrations and mortality rates from some cancers. For example, in a study conducted in Taiwan, there was little to no increase in risk with rising arsenic exposure at low arsenic levels (< 150 µg/L)(Lamm et al., 2013). In another study by Meliker et al., no convincing evidence was found in association between low-level (< 10 µg / L) arsenic exposure and bladder cancer. However, in cases where the concentration of arsenic in drinking water was more than 10 micrograms per liter, bladder cancer were elevated in people aged 30 to 55 whose daily water intake was above average(Meliker et al., 2010).
However, regarding cancer incidence, at low arsenic concentrations positive associations with cancer risk was also reported. For instance, In a review article by Cumberbatch et al., exposure to 10 micrograms per liter of arsenic in drinking water were associated with increased risk of bladder cancer by 2.7 fold (Cumberbatch et al., 2018). Baris et al. in a case-control study in New England also found an association between the incidence of bladder cancer and low arsenic levels in drinking water(Baris et al., 2016). In another cohort study in Canada, a statistically significant relationship was observed between the incidence of bladder cancer and arsenic in drinking water at a concentration more than 5 µg/l(Saint-Jacques et al., 2018).
In addition, in the current study, based on linear regression fitting, the arsenic concentration had a positive association with leukemia cancer, so that, for each unit increase in arsenic concentration in groundwater, the mortality rate of leukemia increases by an average of 0.34(p = 0.033). The highest mortality rate due to leukemia occurred in rural area of Kaboodarahang, where the highest concentrations of arsenic have been reported.
Anamika Basu et.al. in a cross-sectional biomarker study in West Bengal, showed that chronic environmental exposure to arsenic in groundwater causes genotoxic effects, and the micronuclei frequencies in the exposed group were significantly elevated to 5.33-fold over unexposed levels of lymphocytes(Basu et al., 2004).
However, in some epidemiological studies there were no association between leukemia and arsenic concentration. For example, a study by Wu et.al in the southwestern coast of Taiwan, there was no significant dose-response relation between arsenic levels in well water and cancers of the leukemia, esophagus, colon, and stomach(Wu et al., 1989). In another study in Chile, there was little evidence of an increased risk of leukemia, brain, and all childhood cancers and regarding leukemia, the RR for those people their childhood were being exposed to high arsenic contamination in drinking water were below 1.0 (95% CI) for both male and females(Liaw et al., 2008).
One of the reasons for low correlation to leukemia in some previous studies, could be the dual properties of arsenic that has recognized as both drug and poison for more than two thousand years for promyelocytic leukemia(Wang et al., 2020).
In the current study, the minimum ages of mortality from bladder cancer were 54 years old for men and 75 years old in women and the maximum age of mortality from bladder cancer was 92 years old in men and 78 years old in women. Overall, the range of mortality rate from bladder cancer is 54–92 years old.
According to the results, in rural areas of Kaboodarahang, the concentration of arsenic in drinking water and the mortality rate due to bladder and leukemia cancers were significantly higher than other counties. However, among the counties of Hamadan, in Tuyserkan the rate of both bladder and leukemia cancers were high, but the concentration of arsenic in this area was less than the allowable limit (Table 3). Hence, there are other reasons for the high rate of cancers in this county that needs further studies.
Table 3
The number of deaths and mortality rates due to Leukemia and urological cancer
counties
|
Population
|
No. of deaths
Leukemia
|
Mortality rates
(per 100000)
|
No. of deaths
urological cancer
|
Mortality rates (per 100000)
|
Bahar
|
60251
|
3
|
4.979
|
2
|
3.31
|
Kaboodarahang
|
101029
|
11
|
10.887
|
5
|
4.94
|
Malayer
|
100446
|
5
|
4.977
|
4
|
3.98
|
Tuyserkan
|
45453
|
3
|
6.600
|
3
|
6.60
|
Razan
|
80541
|
5
|
6.208
|
2
|
2.48
|
Famenin
|
25151
|
1
|
3.975
|
0
|
0
|
Nahavand
|
85333
|
2
|
2.343
|
1
|
1.17
|
Hamadan
|
98643
|
6
|
6.082
|
1
|
0.101
|
Asadabad
|
42158
|
0
|
0
|
1
|
2.37
|
The results of the present study showed that among the total population of Hamadan province, the risks of mortality of the urological cancer per 100,000 people, were 4.25 for men, and 1.28 for women, respectively. In total, 20% of the mortality rate was related to women and 80% for men. In a study by Chen that conducted in Bangladesh, among the entire population, the mortality rate (per 100,000) for bladder and lung cancer obtained 0.3 and 23.1 for women, and 5.4 and 159.1 for men, respectively. Thus, as can be seen, the rate of bladder cancer in men was recorded 16 fold higher than in women (Chen & Ahsan, 2004). In contrast, in another work by Marshal, the mortality rates of bladder and lung cancer per 100000 were 50 and 153 for men and women in region II (area with high concentration of arsenic), compared with 19 and 54 in other regions(Marshall et al., 2007). According to GLOBOCAN data, in 2018, nations with the highest rates of urological cancer were largely reported in Western and Southern Europe and North America. The highest rate of bladder cancer among women belonged to Lebanon, and in Greece the highest rate was among men. Nevertheless, in the world this type of cancer in male is fourfold higher than female. Tobacco smoking, chemical exposure in workplaces, low fruits and vegetable consumption are the strongest risk factors that are more common in men than women(Saginala et al., 2020). Only 7% of bladder cancer are predicted to rise from heritable genetic influence and 81.8% cases could be attributed to environmental, occupational exposure, and lifestyle. Therefore, this cancer is an optimal candidate for public health prevention interventions(Al-Zalabani et al., 2016).
According to the results, the risks of mortality of the leukemia cancer per 100,000 people were 5.6 overall, and for men and women were 4.56 and 6.76, respectively. The total deaths attributed to leukemia were 41.6% and 58.3% for men and women, respectively. However, this difference in mortality rates between men and women (1.48) is much smaller than the difference in mortality rates of bladder cancer. Among environmental factors, obesity and body mass index have been identified as other risk factors for a variety of leukemia among adult and children(Bhaskaran et al., 2014; Mazzarella et al., 2020). So perhaps, one of the reasons for the higher mortality rate due to leukemia in women, along with other factors, is the higher than the BMI index(Censin et al., 2019). However, there are other factors that contribute to the development of leukemia, including smoking and exposure to chemicals as well as hereditary factors. Globally, the mortality rate of leukemia in males was 4.2 per 100,000 compared to 2.8 per 100,000 in females. In Iran, the mortality rate due to leukemia was reported to be 4.4 in women and 6.6 per 100,000 in men(Bispo et al., 2020).
The minimum and maximum age of mortality due to leukemia among men is 1 and 82 years old, and among women is 4 and 81 years old, and the average of mortality age was 44 years old. Mjali and et al. in Karbala, a total of 402 patients diagnosed with leukemia was retrospectively analyzed during their study. Patients ages were between 1 and 90 years old, and 234 cases were males (58.2%) and 168 were females (41.8%). Among all leukemia cases, 22.6% (n = 91) were under 10 years, and the median age of diagnosis was 30 years for all cases(Mjali et al., 2019). Identifying cancer risk factors play an important role in preventing and controlling them in each region. This study has several limitations. First, some disruptive factors such as diet, obesity, smoking, physical activity and genetic factors were not controlled. In addition, as mentioned earlier, there are several types of arsenic, including As3+, As5+, MMA, and DMA that adversely affect human health. In the present study, the concentration of different types of arsenic has not been determined separately and therefore, it cannot be said which type of arsenic has a significant association with mortality due to cancer.