Arsenic level in bladder tumor of patients from an exposed population: association with progression and prognosis

Future Oncol. 2021 Apr;17(11):1311-1323. doi: 10.2217/fon-2020-0154. Epub 2021 Mar 2.

Abstract

Aims: To elucidate the impact of arsenic on progression and prognosis of bladder cancer. Patients & methods: Total arsenic in 145 tumors (80 non-muscle-invasive [NMIBC] and 65 muscle-invasive bladder cancer [MIBC]) was measured and associated with Ki67 expression, tumor-clinicopathological parameters and patient outcome. Results: Tumor arsenic concentration was higher in exposed than unexposed patients (256 μg/kg vs 77 μg/kg; p < 0.0001) and positively correlated (r = 0.65; p < 0.0001) with arsenic content of patient's drinking water. Arsenic concentration showed significant association with Ki67-overexpression (p = 0.001) and advanced tumor stages (NMIBC vs MIBC; p = 0.0009). In NMIBC, high tumor arsenic (>100 μg/kg) and Ki67 overexpression was established as predictors for recurrence (hazard ratio [HR]: 4.68; p = 0.005 and HR: 3.91; p = 0.018) and progression (HR: 6.04; p = 0.023 and HR: 6.87; p = 0.013). In MIBC, association of high arsenic remained significant with increased risk of recurrence (HR: 4.58; p = 0.04). Conclusion: In NMIBC, high arsenic and Ki67 overexpression and in MIBC, only high arsenic showed prognostic importance in predicting poor patient outcome.

Keywords: West Bengal; bladder cancer; patient outcome; proliferation potential; tumor arsenic.

Plain language summary

Lay abstract Research work suggests arsenic as risk factor for bladder cancer. In developing countries such as India, arsenic contamination of underground drinking water is a major health problem. The present study aimed to evaluate impact of arsenic on parameters of bladder cancer aggressiveness and clinical outcome of patients from West Bengal, India. Our data showed accumulation of arsenic in bladder tumor of patients exposed mainly through contaminated drinking water. Arsenic content in tumor favored aggressive phenotypes in bladder cancer (higher cell proliferation and advanced tumor stages) and was found to be a potential predictor for cases of death and disease recurrence in patients after receiving primary treatment measures. Therefore, arsenic content in bladder tumor may be used to improve existing protocols for better prediction of patient outcomes in populations with a similar type of exposure.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arsenic / metabolism*
  • Biomarkers, Tumor / metabolism
  • Dietary Exposure / adverse effects*
  • Dietary Exposure / analysis
  • Disease Progression
  • Female
  • Humans
  • India
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Survival Analysis
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology
  • Water Pollutants / metabolism*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • MKI67 protein, human
  • Water Pollutants
  • Arsenic