1.Introduction

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Urinary Bladder cancer has a strong association with environmental exposures. This association is particularly strong for arsenic as evident from arsenic induced malignant transformation of human bladder urothelial cells, and correlates to the same endemic areas where populations were identified with arsenic-induced skin cancer [1,2]. Excess inorganic arsenic in drinking water from artesian wells is a major health hazard in certain parts of the world and is associated with an increased risk of urothelialtumors in addition to other diseases [3-5]. Peoples residing in Bengal Delta Plain in India, no comprehensive study has yet been done in this respect considering arsenic as the major risk factor. According to a reported work done by the School of Environmental Studies (SOES), Jadavpur university on ground-water contamination of West Bengal in nine districts (Malda, Murshidabad, Nadia, North-24 Parganas, South-24 Parganas, Barddhaman, Haora, Hugli and Kolkata), are categorized as severely affected (arsenic concentrations > 50 µg/L ) , five districts (Koch Bihar , Jalpaiguri , Darjiling , North Dinajpur and South Dinajpur) as mildly affected (arsenic concentrations 11-50 µg/L) and the rest five districts (Bankura, Birbhum, Purulia, Medinipur East And Medinipur West), as unaffected or arsenic safe (arsenic concentration < 10 µg/L)[6].

We tried to find out if there was any association exists between geographical distribution of bladder carcinoma cases with the reported ground water contamination of Arsenic level in respective districts in West Bengal. Therefore, this study included analysis of arsenic as a risk factor so that avoidance of such factor could decrease the incidence of the disease significantly as well as to designing effective treatment plan for the bladder carcinoma patients.

2.Methods

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It was a retrospective observational survey. In this study we included all the histopathologically proven bladder carcinoma patients. These patients were either operated in our institute or operated elsewhere and then presented to our outpatient department (OPD). Case Report form (CRF) was made for every patient including demographical data, smoking habits, clinical, radiographical and histopathological data. Person residing for a minimum period of 5 year in particular district was considered as resident of that district. We used West Bengal census 2011 data [Table-1] for considering population at risk to calculating incidence-person-year for 2 years from August 2013 to August 2015. We calculated incidence-person-years for every district. We categorised districts according to reported work done by the School of Enviromental Studies, Jadavpur university (SOES) on ground-water contamination of West Bengal6 in three categories – (1) Severely affected, (2) Mildly effected, (3) Safe / Unaffected.

We calculated incidence-person-year in each category. We compared demographical data, smoking habits, staging and grading of tumors between each category. For statistical analysis data were tabulated into a Microsoft excel spreadsheet and then analysed by SPSS 20.0.1 and Graph Pad Prism version 5. Data have been summarized as mean and standard deviation for numerical variables and count and percentages for categorical variables. The median and the inter quartile range have been stated for numerical variables that are not normally distributed. Student’s independent sample’s t-test was applied to compare normally distributed numerical variables between groups; unpaired proportions were compared by Chi-square test or Fisher’s exact test, as appropriate. Confidence interval was 95%.

3.Result

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From August 2013 to August 2015, 279 patients were diagnosed as transitional cell carcinoma of urinary bladder. Out of 279 patients, 242 were from severely affected districts, 28 were from mildly affected districts, and rest of 9 patients from arsenic safe districts.

There was no statistically significant difference (P-value-0.958) between three categories for the gender distribution of cases. We did smoking quantification by pack-year and found that difference between three categories for smoking habits was not statistically significant (P-value-0.965)[Table-2]

There was statistically significant difference between mean age (P-value 0.0009), showed younger age of bladder carcinoma patients in severely affected districts. Mean (±SD) age of the patients was 55.1860 (±6.7081) years [Range: (36.0-73.0)] for severely affected category, 59.28 (±6.6380) years [Range: 43.0-71] for mildly affected districts, and 60.55 (±3.7454) years [Range: (55.0-67.0)]. [Table-2]

Bladder carcinoma incidence in male was more than female in all the three categories of the districts (severely affected category male-0.667, female-0.165), (mild affected category male-0.339, female-0.077), (safe category male-0.064, female-0.019). [Table-1]

Incidence-persons-year was more in severely affected districts (0.211) than the mildly affected (0.106) and safe districts (0.021) categories. Incidence-persons-year was least in arsenic safe category districts. [Table-3]

There was statistically significant difference between diagnosed stage and grade at presentation between three categories (P-value for staging 0.043, and for grade P-value < 0.0001). Patients from the severely affected districts category were diagnosed with higher stage and grade of tumour than the other two categories. [Table-2]

Table1    Table2    Table3

4.Discussion

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Although causal relationships are mostly explained from case-control and cohort studies for known human carcinogens, with little, if any, evidence from ecological studies. But for arsenic in drinking-water, ecological studies provide important information on causal inference, because of large exposure contrasts and limited population migration. Because of widespread exposure to local or regional water sources, ecological measures provide a strong indication of individual exposure and the ecological estimates of relative risk are often so high that potential confounding with known causal factors cannot explain the results [7].

Contamination of groundwater by arsenic was first detected in the West Bengal in one village in the 24-Parganas district; in 1983 (Garai et al., 1984)[8].Since then extensive research in West Bengal has revealed that this region has one of the most serious problems with groundwater contamination by arsenic in wells used for drinking-water [9,10]. Arsenic association with bladder carcinoma was showed in many studies done outside india [11-15], but no study yet been done in this region.

Chiang et al. (1993) showed that the age-adjusted incidence of bladder cancer in the Blackfoot disease-endemic area of Taiwan was higher than that in a neighbouring area of Taiwan and in the country as a whole [16]. Similarly an ecologic study done by Guo et al (1997) using the proportions of wells with various specified arsenic levels in each township as indicators of exposure and evaluated the effects of urbanization and smoking by an urbanization index and the number of cigarettes sold per capita. In both genders, they observed associations of high arsenic levels in drinking water with transitional cell carcinomas of the bladder, kidney, and ureter and all urethral cancers combined. After adjusting for urbanization and age, the proportion of wells with arsenic levels above 0.64 ppm had positive associations with the incidence of transitional cell carcinomas of the bladder, kidney, and ureter and all urethral cancers combined in both genders [17]

Likewise in our study, there was wide variation in bladder carcinoma incidence with level of arsenic contamination. We found more incidence of bladder carcinoma in severely affected districts category than other two districts categories.

According to study done by Steinmaus et al. (2003) of arsenic ingestion and bladder cancer using individual data on water sources, water consumption patterns, smoking, and other factors they found that smokers who drink water containing arsenic at concentrations near 200μg/day may be at increased risk of bladder cancer compared with smokers at lower arsenic exposures [18].

Likewise in our study we found no statistically significant difference for smoking habits between three categories but there was high incidence of bladder carcinoma in severely affected districts category than the other two categories. It showed that in these districts arsenic might be the major risk factor for causing bladder carcinoma. As majority of the population in this region is smoker, there might be some additive effect of arsenic with other risk factors like smoking, which may be the cause of such a high incidence of bladder carcinoma in this region.

In this study we found that bladder carcinoma incidence was highest in severely affected districts than the other two categories, also in these districts bladder carcinoma presented in comparatively in younger age group and with higher stage and grade. So according to our study we found that bladder carcinoma in severely affected districts were more aggressive than the other two categories.

Further studies needed to evaluate the role of arsenic as a risk factor for urinary bladder carcinoma, role of individual metabolic system to handling arsenic because although all the person exposed to arsenic in a particular district, but not everyone developed urinary bladder carcinoma. Further studies also needed to evaluate cellular and molecular changes that are responsible for inducing carcinoma because of arsenic.

Limitations of this study were that it was an ecological study, so definitive causal relationship could not be measured. Although our institute drained most of the patients in this region but further studies will be needed at larger scale.

5.Conclusion

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Arsenic contamination seems major risk factor for causing high incidence of bladder carcinoma in this region. From our study we conclude that arsenic induced bladder carcinoma are comparatively more aggressive as presenting in early age with higher grade and stage. Further studies needed to established causal relationship of arsenic contamination with bladder carcinoma, cellular and molecular changes in arsenic induced bladder carcinoma.