BCAN TT 2022: Exposures to Environmental Contaminants as Important Risk Factors for Bladder Cancer: Existing Knowledge and Future Research Needs

(UroToday.com) Dr. Joshua Meeks, a urologic oncologist at Northwestern University Feinberg School of Medicine, and Carsten Prasse, Ph.D., MS, an Assistant Professor of Environmental Health and Engineering from Johns Hopkins University co-chaired a breakout session dedicated to the role of environmental contaminants in bladder cancer pathogenesis. They were joined by discussion leaders Dr. Stella Koutros, Ph.D., MPH from the National Cancer Institute, Molly Jacobs, MPH from the Lowell Center for Sustainable Production, and Dr. Sunil Patel, MD, a urologic oncologist from the Brady Urologic Institute at Johns Hopkins University. The goal of the session was to describe what is known about environmental carcinogens, how they cause cancer, characterize limitations in our current knowledge, and discuss mitigation strategies to decrease the risk of bladder cancer from environmental exposures.

When an individual experiences either an incidental environmental exposure or occupational exposure to a carcinogen, the context, and level of the exposure is important to quantify and contextualize. There have been a number of suspected or established carcinogens linked to bladder cancer through epidemiological studies, including the New England Bladder Cancer Study (NEBCS) as well as the Spanish EPICURIO study.  

Many ongoing investigative efforts are led by the NCI Division of Cancer Epidemiology and Genetics. While smoking is the main risk factor for developing bladder cancer, occupational exposure can be attributable in 25% of men and 11% of women.

A high-risk occupational exposure population recently appreciated is firefighters. The International Agency for Research on Cancer (IARC) has recognized sufficient evidence to link a number of occupational exposures suffered by firefighters with developing both lung and bladder cancers. Other environmental exposures recently linked to the development of bladder cancer include diesel exhaust, arsenic and nitrate contamination of drinking water, metalworking fluids, solvents (paint, varnishes, adhesives, glues), and disinfection by-products (DBP) from water disinfection. These data have been implemented in the concept of the “exposome”- the cumulative measure of environmental influences and biological responses throughout one’s life. Investigators at the NCI are also conducting GWAS to identify common genetic variability that increases risk to these carcinogens. 

Per- and polyfluoroalkyl substances (PFAS) have been used since the 1950s in common products, including non-stick cookware, outdoor gear and food packaging. PFAS are found ubiquitously in the environment in the US, especially around military training areas. In fact, PFAS can be detected in urine samples from >98% of the US population. Common mitigation strategies to limited ingestion exposure include avoiding plastic water bottles and using water filters specifically designed to eliminate PFAS. While links between PFAS and bladder cancer have been suggested, there are no confirmatory studies at present time.

There are many known bladder cancer-causing chemicals present in cigarette smoke, and these chemicals are present but in lower concentrations in e-cigarettes. Notably, however, the majority of chemicals in e-cigarette aerosols are uncharacterized and may pose a considerable carcinogenic risk.

Bisphenol A (BPA) is a synthetic monomer used in the manufacturing of polycarbonate plastics. It is commonly found in consumer products and has potent estrogen receptor agonist properties. The presence of hormone rectors in the urothelium has been proposed as a mechanism for BPA bladder cancer carcinogenesis.

A pilot study investigating BPA association with bladder cancer was led by Dr. Patel. They used reverse-phase liquid chromatography and mass spectrometry to measure BPA in 20 bladder cancer patients, 20 prostate cancer patients, and 20 healthy controls. All patients had BPA in their urine, but the bladder cancer patients had significantly higher levels than the other two cohorts.

We are in obvious need of a comprehensive investigation of BPA and PFAS as potential carcinogens for urologic cancer, and this is likely to require large-scale, multidisciplinary action.

Lastly, the panel discussed the role of preventative measures with respect to occupational and environmental exposures. The concept of intervention research was proposed, which moves from knowledge to action by studying solutions to problems identified in conventional etiologic research efforts.

 

BCAN Think Tank 2022_Joshua Meeks_3 

Prevention requires action on multiple levels. First, at the individual level, one mitigates their own risk through proactive measures not otherwise regulated at the state or federal level (ex. smoking cessation). Second, at the institutional level, efforts are focused on eliminating or substituting bladder carcinogens with safer alternatives. Consumers can use purchasing power to influence change at the institutional level. Lastly, the policy level is driven by environmental and occupational regulations.

Lasting impact is likely to require multilevel interventions. The next logical step after identifying specific bladder cancer carcinogens is to characterize their role in stage migration, therapeutic response and long term oncologic outcomes.

 

Presented by: Joshua Meeks, urologic oncologist at Northwestern University Feinberg School of Medicine; MD, PhD, Carsten Prasse, PhD, MS, Assistant Professor of Environmental Health and Engineering from Johns Hopkins University Dr. Stella Koutros, PhD, MPH from the National Cancer Institute; Molly Jacobs, MPH from the Lowell Center for Sustainable Production, and Dr. Sunil Patel, MD, urologic oncologist from the Brady Urologic Institute at Johns Hopkins University

Written by: Patrick Hensley, MD, Urologic Oncologist at the University of Kentucky (@pjhensley11) with Ashish Kamat, MD, Urologic Oncologist at MD Anderson Cancer Center (@UroDocAsh) during the 2022 Bladder Cancer Advocacy Network Think Tank (#BCANTT22) Wednesday, Aug 3 – Friday, Aug 5, 2022

References:

1. Demers PA, DeMarini DM, Fent KW, et al. Carcinogenicity of occupational exposure as a firefighter. Lancet Oncol. 2022 Aug;23(8):985-986. doi: 10.1016/S1470-2045(22)00390-4. Epub 2022 Jul 1. PMID: 35780778.
2. Miller GW, Jones DP. The nature of nurture: refining the definition of the exposome. Toxicol Sci. 2014 Jan;137(1):1-2. doi: 10.1093/toxsci/kft251. Epub 2013 Nov 9. PMID: 24213143; PMCID: PMC3871934.
3. Tehrani MW, Newmeyer MN, Rule AM, et al. Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography-High-Resolution Mass Spectrometry. Chem Res Toxicol. 2021 Oct 18;34(10):2216-2226. doi: 10.1021/acs.chemrestox.1c00253. Epub 2021 Oct 5. PMID: 34610237.
4. Patel SH, Metcalf M, Bivalacqua TJ, et al. Plastic exposure and urological malignancies - an emerging field. Nat Rev Urol. 2020 Dec;17(12):653-654. doi: 10.1038/s41585-020-00385-6. PMID: 33028980.

 

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