Page 95 - JCTR-11-3

Journal of Clinical and
Translational Research Household arsenic and bladder cancer

1. Introduction from the same clinic with benign urologic disease (kidney
stones, benign prostatic hyperplasia, urinary incontinence)
Urothelial cell carcinomas (UCCs) represent the majority of and were recruited to be comparable in age, sex, and race
human bladder tumors and are considered environmental to UCC patients. All enrolled patients were self-reported
1
cancers. Cigarette smoking accounts for approximately current non-smokers (never smokers or former smokers
2
50% of bladder cancer cases in both men and women, with who had quit at least 12 months prior). 19
3
2 – 8% of cases attributed to occupational exposures. 1,4,5
However, about one-third of bladder cancer cases in the All study procedures were approved by the University
United States remain unexplained by these known risk of Wisconsin–Madison Institutional Review Board
factors. (protocol number 2022-1030-CP002), and all patients
provided written informed consent. Voided urine samples
The incidence of UCC is higher among individuals (minimum 15 mL) were collected from each patient,
6-8
from lower socioeconomic strata, even independent either as leftover specimens from routine urinalysis or
9,10
of smoking status, though the underlying reasons for through home collection. Patients were also provided a
this disparity are not fully understood. UCC risk is also kit containing a questionnaire and materials to collect
elevated in populations living in areas of higher industrial drinking water and household dust samples. For water
activity, which may lead to increased environmental sampling, patients were asked to collect a sample from
1,11
exposure to pollutants in soil, water, or air, including their primary drinking water source using a provided
known bladder carcinogens such as arsenic and acrolein. 4-ounce plastic bottle. Tap water was run for 2 min before
2,12
Inorganic arsenic (iAs) is found in air pollution, second- sample collection; bottled or fridge-filtered water was
hand tobacco smoke, contaminated drinking water, certain collected directly. For dust sampling, patients received
foods, and even household dust. 13-15 Acrolein is present in disposable gloves, a 25 cm × 25 cm paper template, and
automobile exhaust, industrial emissions, second-hand a Ghost Wipe (SKC Inc.), with instructions to collect
smoke, wood fires, cooking fumes, and fried foods. dust from the threshold of the primary bedroom after
16
However, urinary arsenic and acrolein exposures have not refraining from vacuuming for 1 week. Dust wipes were
been evaluated in individual bladder cancer patients in the placed in 50 mL conical tubes. All samples were returned
United States. to the principal investigator’s laboratory through overnight
We recently found that all 42 primarily non-smoking mail in a postage-paid box.
healthy adults in a previous study had measurable urinary
exposures to iAs and acrolein, with some reaching 2.2. Chemical assays
genotoxic concentrations as assessed in vitro using primary Chemical analyses were performed at the Wisconsin State
and immortalized urothelial cells. 17,18 Furthermore, these Laboratory of Hygiene at the University of Wisconsin–
urinary exposures correlated with those in their pet dogs, Madison. Urinary acrolein exposure was quantitated by
suggesting household, rather than occupational, sources measuring its stable 3-hydroxy-propyl-mercapturic acid
for these environmental chemicals. 17 (3-HPMA) metabolite, using liquid chromatography-
20
We hypothesized that household exposures to arsenic electrospray ionization-mass spectrometry. Total arsenic
and acrolein contribute to non-tobacco, non-occupational was measured in dust and drinking water, while iAs
UCC risk. The aims of this study were to determine species – including arsenite, arsenate, monomethylarsonic
whether urinary and household exposures to acrolein acid, dimethylarsinic acid, and trimethylarsine oxide
and iAs are higher in patients with newly diagnosed UCC – were measured in urine using liquid chromatography-
14
compared to those with benign urologic disease, to assess inductively coupled plasma-mass spectrometry. Urinary
whether urinary concentrations reach genotoxic urothelial cotinine was included as a marker of active smoking or
21
thresholds, and to characterize urinary and household second-hand tobacco smoke exposure. Concentrations
chemical exposures by urbanicity and area deprivation of all urinary chemicals were normalized to urinary
indices. creatinine (creat) to control for individual differences in
urine concentration. Arsenic concentrations in household
17
2. Methods dust were normalized to the sampled surface area.
2.1. Patient recruitment 2.3. Questionnaires

Patients with a biopsy-confirmed diagnosis of superficial Patients were asked to complete a questionnaire addressing
or muscle-invasive UCC were enrolled from the urology demographic information (age range by decade, sex, race,
clinic at the teaching hospital of the University of and current/previous occupations), as well as household
Wisconsin–Madison (UWHealth). Controls were patients factors relevant to acrolein and arsenic exposures.

Volume 11 Issue 3 (2025) 89 doi: 10.36922/jctr.24.00065