Urologic oncologist Kyle Richards, MD, FACS, of the Department of Urology at the University of Wisconsin School of Medicine and Public Health (UW SMPH) and Lauren Trepanier, DVM, PhD, DACVIM (SAIM), of the UW School of Veterinary Medicine, are collaborating on a groundbreaking research study titled “Non-Tobacco, Non-Occupational Chemical Exposures and Bladder Cancer Risk across Socioeconomic Strata.” Using a novel, dual-species approach, Drs. Richards and Trepanier are examining environmental exposures in both humans and dogs to two chemicals, acrolein and inorganic arsenic, to learn if there is an association between those exposures and bladder cancer risk.
Currently, about 50% of patients with bladder cancer are smokers or former smokers. Occupational industrial exposures are associated with another roughly 30% of bladder cancer cases – but the remaining cases are largely unexplained. Further, despite the dramatic decline in smoking rates in the United States over the past 20 years, rates of bladder cancer have remained static. “We would have expected to see a decline in bladder cancer,” says Dr. Richards, “but we haven’t,” adding:
“It’s not infrequent that I’m seeing a patient nowadays who is newly diagnosed with bladder cancer, and they ask, ‘Well, how did I get this? What did I do? I didn’t smoke, I didn’t drink, I led a pretty clean lifestyle.’ More and more patients are coming to clinic with those questions, and I think the onus is on us to figure this out.”
Thus, when Dr. Richards learned about Dr. Trepanier’s bladder cancer research with dogs, he immediately saw “parallels with the kind of work that could be done looking at humans.”
Why dogs?
Canine companions not only share the same living environment as their human counterparts, but when dogs develop bladder cancer, the disease is very similar to the most aggressive type of bladder cancer in humans and occurs at an earlier absolute age. While conducting one of a number of her studies on environmental exposures in dogs with cancer, Dr. Trepanier came across an opportunity to write an Institute for Clinical and Translational Research (ICTR) pilot grant. She viewed this pilot as a chance to expand her bladder cancer research to include human subjects, reaching out to the UW Department of Urology and subsequently to Dr. Richards to collaborate on the study. Together, they would seek to answer the question:
In people who are currently non-smokers, can we identify household chemicals that are associated with bladder cancer risk?
Study Approach
Dr. Richards, with help from UW endourologist Dr. Margaret Knoedler, is recruiting 25 nonsmoking patients who are newly diagnosed with bladder cancer and 25 patients who do not have cancer to function as a control group. For the canine part of the study, the team is measuring chemicals in dogs with and without bladder cancer across the country, as well as in their owners, “with the hypothesis that if you live with a dog with bladder cancer, you may have higher urinary chemical exposure than, say, the owner of a dog who’s very similar, who does not have bladder cancer,” explains Dr. Trepanier.
The team is specifically looking at acrolein and inorganic arsenic in their subjects’ urine and inorganic arsenic in the dust and water in these households. For the dogs only, the team is also measuring airborne acrolein levels in the house. Acrolein is a known urothelial carcinogen typically found in cigarette smoke, indoor air pollution, and even in fried foods, but acrolein metabolites have not been looked at previously in bladder cancer patients.
The study design involves patient biomonitoring and additional in vitro tests to determine if subjects reach DNA damaging concentrations of these chemicals in their urine, and whether this is more common in the bladder cancer cases than in the controls. The team will then use findings from this ICTR pilot grant-funded research to determine if enough of an association exists to justify a larger study.
Potential Impacts
Looking ahead to possible long-term impacts of their research, Dr. Richards and Dr. Trepanier are excited about the potential for evidence-based preventative measures emerging from their work. For example, if they demonstrate an association between acrolein exposure and bladder cancer in people, they can advise newly diagnosed patients to minimize cooking foods at high heat with oil and using fireplaces – while ensuring they have good indoor ventilation to prevent further exposure to acrolein. If they see an association with arsenic, they could recommend that those who are diagnosed with or are at familial risk of getting bladder cancer get water filtration units that are rated to filter for arsenic.
Ultimately, the team hopes that their novel approach – combining human and canine subjects – will allow them to take a significant leap forward in understanding environmental links to bladder cancer while pioneering a path toward improved diagnostics and preventative measures for a complex and often elusive disease.
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Drs. Trepanier and Richards are conducting this research with limited pilot funds, and they have many other questions they want to answer. If you are interested in helping to support their work, please contact Christina Marcinske to find out how you can get involved.