AccScience Publishing / JCTR / Online First / DOI: 10.36922/jctr.24.00065
ORIGINAL ARTICLE

Household arsenic and acrolein exposures and risk of urothelial cell carcinoma

Hannah Peterson1 Kyle A. Richards2 Tudor Borza2 Abigail M. Wiedmer2 Maria T. Jabbour2 Margaret A. Knoedler2 Erin Mani3 Christa Dahman3 Lauren Trepanier1*
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1 Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
2 Department of Urology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
3 Wisconsin State Laboratory of Hygiene, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
Received: 28 September 2024 | Revised: 8 January 2025 | Accepted: 16 April 2025 | Published online: 21 May 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Background: Smoking accounts for about half of bladder cancer cases in the United States; however, the etiology of up to one-third of urothelial cell carcinoma (UCC) remains poorly understood. Acrolein and arsenic are known bladder carcinogens with documented household exposures. Aim: This study aimed to (i) determine whether urinary and household exposures to acrolein and inorganic arsenic (iAs) are higher in newly diagnosed UCC patients than in those with benign urologic disease, (ii) assess whether urinary concentrations reach genotoxic thresholds, and (iii) evaluate how these exposures vary by urbanicity and area deprivation indices. Methods: Patients were recruited from the Urology Clinic at the University of Wisconsin–Madison and provided urine, drinking water, and household dust samples. Results: Acrolein exposures (as its stable metabolite 3-hydroxy-propyl-mercapturic acid) did not differ between cases and controls. Urinary arsenic concentrations were higher in cases than in controls but did not reach statistical significance (p=0.08). Unadjusted urinary iAs concentrations (reflecting urothelial exposures) ranged from 0.01 to 0.71 μM in cases and 0.02 – 0.14 μM in controls (p=0.05). No patients reached genotoxic urinary concentrations of iAs (10 μM) at a single time point. Arsenic concentrations in household dust were higher in UCC (0.42 ng/cm2) compared to control households (0.29 ng/cm2; p=0.007). Dust arsenic levels also correlated with urinary iAs across all patients (r = 0.41; p=0.004). Drinking water arsenic was associated with higher area deprivation percentiles (r = 0.30, p=0.046) and with households from more rural areas (p=0.039) but did not differ significantly between cases and controls. Conclusion: Our data suggest that indoor dust arsenic, rather than arsenic in drinking water, was a likely source of urinary arsenic exposure in this primarily non-smoking population. Relevance for patients: Simple in-home arsenic mitigation strategies, such as using high-efficiency particulate air vacuum cleaners and air filtration units, may help reduce exposure for patients diagnosed with UCC.

Keywords
Bladder cancer
Non-smokers
Household dust
Inorganic arsenic
Drinking water
Funding
This work was supported by a pilot grant from the University of Wisconsin–Madison Institute for Clinical and Translational Research, funded by UL1TR002373 from NIH/NCATS. Tudor Borza is supported by AHRQ career development award K08HS028474.
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Letasiova S, Medve’ova A, Sovcikova A, et al. Bladder cancer, a review of the environmental risk factors. Environ Health. 2012;11 Suppl 1:S11. doi: 10.1186/1476-069X-11-S1-S11

 

  1. Cumberbatch MGK, Jubber I, Black PC, et al. Epidemiology of bladder cancer: A systematic review and contemporary update of risk factors in 2018. Eur Urol. 2018;74(6):784-795. doi: 10.1016/j.eururo.2018.09.001

 

  1. Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC. Association between smoking and risk of bladder cancer among men and women. JAMA. 2011;306(7):737-745. doi: 10.1001/jama.2011.1142

 

  1. Vineis P, Simonato L. Proportion of lung and bladder cancers in males resulting from occupation: A systematic approach. Arch Environ Health. 1991;46(1):6-15. doi: 10.1080/00039896.1991.9937423

 

  1. Czerniak B, Dinney C, McConkey D. Origins of bladder cancer. Annu Rev Pathol. 2016;11:149-174. doi: 10.1146/annurev-pathol-012513-104703

 

  1. Hoebel J, Kroll LE, Fiebig J, et al. Socioeconomic inequalities in total and site-specific cancer incidence in Germany: A population-based registry study. Front Oncol. 2018;8:402. doi: 10.3389/fonc.2018.00402

 

  1. Bryere J, Dejardin O, Launay L, et al. Socioeconomic status and site-specific cancer incidence, a Bayesian approach in a French Cancer Registries Network study. Eur J Cancer Prev. 2018;27(4):391-398. doi: 10.1097/CEJ.0000000000000326

 

  1. O’Meara S, Bhatt NR, Flynn RJ, Manecksha RP, Thomas AZ. Bladder cancer in Ireland: A 21-year review. Ir J Med Sci. 2021;190(2):531-538. doi: 10.1007/s11845-020-02318-z

 

  1. Goy J, Rosenberg MW, King WD. Health risk behaviors: Examining social inequalities in bladder and colorectal cancers. Ann Epidemiol. 2008;18(2):156-162. doi: 10.1016/j.annepidem.2007.09.004

 

  1. Densmore R, Hajizadeh M, Hu M. Trends in socio-economic inequalities in bladder cancer incidence in Canada: 1992- 2010. Can J Public Health. 2019;110(6):722-731. doi: 10.17269/s41997-019-00227-y

 

  1. Hayes HM Jr., Hoover R, Tarone RE. Bladder cancer in pet dogs: A sentinel for environmental cancer? Am J Epidemiol. 1981;114(2):229-233. doi: 10.1093/oxfordjournals.aje.a113186

 

  1. Lee HW, Wang HT, Weng MW, et al. Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells. Oncotarget. 2014;5(11):3526-3540. doi: 10.18632/oncotarget.1954

 

  1. Hysong TA, Burgess JL, Cebrian Garcia ME, O’Rourke MK. House dust and inorganic urinary arsenic in two Arizona mining towns. J Expo Anal Environ Epidemiol. 2003;13(3):211-218. doi: 10.1038/sj.jea.7500272

 

  1. Chung JY, Lim HJ, Kim YJ, Song KH, Kim BG, Hong YS. The separation of arsenic metabolites in urine by high performance liquid chromatographyinductively coupled plasma-mass spectrometry. Environ Health Toxicol. 2014;29:e2014018. doi: 10.5620/eht.e2014018

 

  1. Saint-Jacques N, Parker L, Brown P, Dummer TJ. Arsenic in drinking water and urinary tract cancers: A systematic review of 30 years of epidemiological evidence. Environ Health. 2014;13:44. doi: 10.1186/1476-069X-13-44

 

  1. Stevens JF, Maier CS. Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol Nutr Food Res. 2008;52(1):7-25. doi: 10.1002/mnfr.200700412

 

  1. Craun K, Luethcke KR, Shafer M, et al. Environmental chemical exposures in the urine of dogs and people sharing the same households. J Clin Transl Sci. 2020;5(1):e54. doi: 10.1017/cts.2020.548

 

  1. Peterson H, Holler J, Boswell A, Trepanier L. Urothelial genotoxicity of environmental chemicals detected in the urine of healthy dogs and their owners. J Clin Transl Sci. 2024;8:e174. doi: 10.1017/cts.2024.546

 

  1. Al-Zalabani AH, Stewart KF, Wesselius A, Schols AM, Zeegers MP. Modifiable risk factors for the prevention of bladder cancer: A systematic review of meta-analyses. Eur J Epidemiol. 2016;31(9):811-851. doi: 10.1007/s10654-016-0138-6

 

  1. Watzek N, Scherbl D, Feld J, et al. Profiling of mercapturic acids of acrolein and acrylamide in human urine after consumption of potato crisps. Mol Nutr Food Res. 2012;56(12):1825-1837. doi: 10.1002/mnfr.201200323

 

  1. Haufroid V, Lison D. Urinary cotinine as a tobacco-smoke exposure index: A minireview. Int Arch Occup Environ Health. 1998;71(3):162-168. doi: 10.1007/s004200050266

 

  1. Zuelsdorff M, Larson JL, Hunt JFV, et al. The Area Deprivation Index: A novel tool for harmonizable risk assessment in Alzheimer’s disease research. Alzheimers Dement (N Y). 2020;6(1):e12039. doi: 10.1002/trc2.12039

 

  1. Kind AJH, Buckingham WR. Making neighborhood-disadvantage metrics accessible - the neighborhood atlas. N Engl J Med. 2018;378(26):2456-2458. doi: 10.1056/NEJMp1802313

 

  1. Blansky D, Mantzaris I, Rohan T, Hosgood HD 3rd. Influence of rurality, race, and ethnicity on non-hodgkin lymphoma incidence. Clin Lymphoma Myeloma Leuk. 2020;20(10):668- 676.e5. doi: 10.1016/j.clml.2020.05.010

 

  1. USDA. USDA Rural-Urban Continuum Codes. U.S. Department of Agriculture ERS; 2023. Available from: https://ed.ers.usda.gov [Last accessed on 2024 Jul 15].

 

  1. Cohen SM, Garland EM, St John M, Okamura T, Smith RA. Acrolein initiates rat urinary bladder carcinogenesis. Cancer Res. 1992;52(13):3577-3581.

 

  1. Cohen SM, Ohnishi T, Arnold LL, Le XC. Arsenic-induced bladder cancer in an animal model. Toxicol Appl Pharmacol. 2007;222(3):258-263. doi: 10.1016/j.taap.2006.10.010

 

  1. Chung CJ, Pu YS, Su CT, et al. Polymorphisms in one-carbon metabolism pathway genes, urinary arsenic profile, and urothelial carcinoma. Cancer Causes Control. 2010;21(10):1605-1613. doi: 10.1007/s10552-010-9589-3

 

  1. Huang YK, Huang YL, Hsueh YM, et al. Arsenic exposure, urinary arsenic speciation, and the incidence of urothelial carcinoma: A twelve-year follow-up study. Cancer Causes Control. 2008;19(8):829-839. doi: 10.1007/s10552-008-9146-5

 

  1. Chai CY, Huang YC, Hung WC, Kang WY, Chen WT. Arsenic salt-induced DNA damage and expression of mutant p53 and COX-2 proteins in SV-40 immortalized human uroepithelial cells. Mutagenesis. 2007;22(6):403-408. doi: 10.1093/mutage/gem035

 

  1. Liao YC, Chen YF, Lee TC. Increased susceptibility of H-Ras(G12V)-transformed human urothelial cells to the genotoxic effects of sodium arsenite. Arch Toxicol. 2015;89(11):1971-1979. doi: 10.1007/s00204-014-1344-1

 

  1. Holcomb N, Goswami M, Han SG, et al. Inorganic arsenic inhibits the nucleotide excision repair pathway and reduces the expression of XPC. DNA Repair (Amst). 2017;52:70-80. doi: 10.1016/j.dnarep.2017.02.009

 

  1. Ibanez-Del Rivero C, Fry KL, Gillings MM, Barlow CF, Aelion CM, Taylor MP. Sources, pathways and concentrations of potentially toxic trace metals in home environments. Environ Res. 2023;220:115173. doi: 10.1016/j.envres.2022.115173

 

  1. Doyi INY, Strezov V, Isley CF, Yazdanparast T, Taylor MP. The relevance of particle size distribution and bioaccessibility on human health risk assessment for trace elements measured in indoor dust. Sci Total Environ. 2020;733:137931. doi: 10.1016/j.scitotenv.2020.137931

 

  1. Liu Y, Ma J, Yan H, et al. Bioaccessibility and health risk assessment of arsenic in soil and indoor dust in rural and urban areas of Hubei province, China. Ecotoxicol Environ Saf. 2016;126:14-22. doi: 10.1016/j.ecoenv.2015.11.037

 

  1. Fazlzadeh M, Salarifar M, Hassanvand MS, Nabizadeh R, Shamsipour M, Naddafi K. Health benefits of using air purifier to reduce exposure to PM-bound polycyclic aromatic hydrocarbons (PAHs), heavy metals and ions. J Clean Prod. 2022;352:131457. doi: 10.1016/j.jclepro.2022.131457

 

  1. Roy A, Jha AK, Kumar A, et al. Heavy metal pollution in indoor dust of residential, commercial, and industrial areas: A review of evolutionary trends. Air Qual Atmos Health. 2024;17(4):891-918. doi: 10.1007/s11869-023-01478-y

 

  1. Nigra AE, Chen Q, Chillrud SN, et al. Inequalities in public water arsenic concentrations in counties and community water systems across the United States, 2006-2011. Environ Health Perspect. 2020;128(12):127001. doi: 10.1289/EHP7313

 

  1. Nigra AE, Cazacu-De Luca A, Navas-Acien A. Socioeconomic vulnerability and public water arsenic concentrations across the US. Environ Pollut. 2022;313:120113. doi: 10.1016/j.envpol.2022.120113

 

  1. EPA. National Primary Drinking Water Regulations; Arsenic and Clarifications to Compliance and New Source Contaminants Monitoring. EPA. Available from: https:// federalregister.gov2001 [Last accessed on 2024 Jul 01].

 

  1. Smith AH, Goycolea M, Haque R, Biggs ML. Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water. Am J Epidemiol. 1998;147(7):660-669. doi: 10.1093/oxfordjournals.aje.a009507

 

  1. Hong JH, Lee PAH, Lu YC, et al. Acrolein contributes to urothelial carcinomas in patients with chronic kidney disease. Urol Oncol. 2020;38(5):465-475. doi: 10.1016/j.urolonc.2020.02.017

 

  1. Gilbert NL, Guay M, David Miller J, Judek S, Chan CC, Dales RE. Levels and determinants of formaldehyde, acetaldehyde, and acrolein in residential indoor air in Prince Edward Island, Canada. Environ Res. 2005;99(1):11-17. doi: 10.1016/j.envres.2004.09.009

 

  1. Marcham CL, Springston JP. Electronic cigarettes in the indoor environment. Rev Environ Health. 2019;34(2):105-124. doi: 10.1515/reveh-2019-0012

 

  1. Seaman VY, Bennett DH, Cahill TM. Origin, occurrence, and source emission rate of acrolein in residential indoor air. Environ Sci Technol. 2007;41(20):6940-6946. doi: 10.1021/es0707299

 

  1. Chung CJ, Lee HL, Chang CH, et al. Measurement of urinary arsenic profiles and DNA hypomethylation in a case-control study of urothelial carcinoma. Arch Toxicol. 2019;93(8):2155-2164. doi: 10.1007/s00204-019-02500-y

 

  1. Villanueva CM, Cantor KP, Grimalt JO, et al. Bladder cancer and exposure to water disinfection by-products through ingestion, bathing, showering, and swimming in pools. Am J Epidemiol. 2007;165(2):148-156. doi: 10.1093/aje/kwj364

 

  1. Guo J, Villalta PW, Weight CJ, et al. Targeted and untargeted detection of DNA adducts of aromatic amine carcinogens in human bladder by ultra-performance liquid chromatography-high-resolution mass spectrometry. Chem Res Toxicol. 2018;31:1382-1397. doi: 10.1021/acs.chemrestox.8b00268

 

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