Abstract

Exposure to toxic inorganic Arsenic (iAs) in areas endemic for urogenital schistosomiasis may confer increased risk for bladder cancer. The severity of the adverse effects of iAs however depends on its metabolism, which is highly variable among individuals. Genetic polymorphism in Arsenic (+3) Methyl Transferase enzyme, accounts significantly for these variations. To investigate the relationship of AS3MT gene polymorphisms and Arsenic metabolism to schistosomiasis and/or associated bladder pathology, 119 individualsfrom Eggua in southwest Nigeria were recruited for this study. Screening for schistosomiasis and bladder pathology was done by microscopy and ultrasonography respectively. Wagtech Digital Arsenator was used to assess total urinary arsenic concentrations and thus determine the level of arsenic exposure. The single nucleotide polymorphism AS3MT/Met287Thr T>C (rs11191439) was genotyped using Alelle-Specific PCR. Of the participants who tested positive for schistosomiasis, 33.3% exhibited bladder pathology. Total urinary arsenic concentration in 80% of the participants was above the WHO limit of 0.05mg/L. The Met287Thr allelic distribution conformed to the Hardy-Weinberg equilibrium (X2= 0.161, P> 0.05). Observed allelic frequencies were 0.96 and 0.04 for wild-type T and mutant C alleles respectively. There was no significant relationship between AS3MT SNP, arsenic concentrations and schistosomiasis associated bladder pathology. In conclusion, the community is highly exposed to arsenic, although with a possible genetic advantage of increased AS3MT catalytic activity. However, we see the need for urgent intervention as inter-individual differences in arsenic metabolism may influence the bladder pathology status of individuals in the community. And although urogenital schistosomiasis is waning in Eggua, it is not known what synergy the infection and high arsenic exposure may wield on bladder pathology.

Highlights

  • Schistosoma haematobium is a biological carcinogen implicated in a large number of bladder cancer cases in Africa and Middle East (Mbanefo et al, 2018)

  • About 120 million cases of S. haematobium infection causing urogenital schistosomiasis (UGS) have been reported in sub-Saharan Africa, with high infection prevalence localised in rural communities

  • We recently reported a concordance in exposure to inorganic Arsenic (iAS) and UGS infection in Eggua, Nigeria (Bakare et al, 2018)

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Summary

Introduction

Schistosoma haematobium is a biological carcinogen implicated in a large number of bladder cancer cases in Africa and Middle East (Mbanefo et al, 2018). Increased risk for bladder cancer associated with S. haematobium infection could come from the progression of schistosomiasis associated bladder pathologies or the occurrence of more severe pathologies (Honeycutt et al, 2014 and Onile et al, 2016). Chronic exposure to inorganic (iAs) through contaminated drinking water has been identified as one of the important risk factors associated with bladder cancer in areas not endemic to schistosomiasis but where untreated underground water is being consumed (D’lpplotti et al, 2015). 140 million people in 50 countries (including some in Africa), consume inorganic Arsenic (iAS) in contaminated drinking water at concentrations that exceed the World Health Organization’s recommended standard of 0.01mg/L (WHO, 2018). The aim of this study was to investigate the association between AS3MT gene polymorphisms and total urinary arsenic concentrations in relation to schistosomiasis associated bladder pathology in the study population

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