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Gut Microbes Implicated In Bladder Cancer
At any given time, over 10 trillion microbes call our guts their home. From breaking down nutrients in our food to strengthening our immunity against pathogens, these microbes play an essential role in how we interact with the world. This includes—as shown in a new study by EMBL researchers and collaborators at the University of Split, Croatia—the way the body responds to carcinogens and develops cancer. The research is published in the journal Nature.
Carcinogens are chemicals that can cause ordinary cells to transform into cancer cells, giving rise to tumors and cancer. They can be found in a number of places, tobacco smoke being one of the most well-known sources.
Researchers have previously found that if mice are exposed to the nitrosamine BBN, one of the chemicals found in tobacco smoke, they reliably develop an aggressive form of bladder cancer. This is therefore used as a common laboratory model of carcinogen-induced cancer.
Janoš Terzić's lab at the University of Split, Croatia, was studying this model when they made a curious observation. If the mice were fed antibiotics, at a dose that kills 99.9% of their gut bacteria, at the same time as they were exposed to BBN the chances of them forming tumors were much lower.
"While 90% of mice exposed to BBN went on to develop bladder tumors, only 10% of those that also received antibiotics did so. This led us to hypothesize that the gut bacteria might be involved in regulating the way BBN is processed in the body," said Blanka Roje, co-first author of the study and Ph.D. Student at the Laboratory for Cancer Research, University of Split School of Medicine in Croatia.
"I'll never forget seeing BBN and BCPN bands on thin layer chromatography plates following overnight incubation of bacteria and BBN."
"The decrease in tumor incidence was so dramatic that at first I doubted the results, thinking we must have made a mistake somewhere in the experiment. Consequently, we repeated the experiment five times before we finally became 'believers,'" Terzić said.
"It was fantastic to realize that with a treatment—in this case, antibiotics—we were able to abolish cancer development."
While attending a conference at EMBL Heidelberg, Terzić met with Michael Zimmermann, a group leader at EMBL Heidelberg. The Zimmermann group specializes in using high-throughput methods to study gut microbiome functions, focusing mainly on a process called biotransformation. Biotransformation is the ability microorganisms have to alter or break down chemicals in their environment.
The initial meeting gave rise to a fruitful collaboration. The two groups decided to combine their expertise to understand whether and how gut bacteria affected the way the mice responded to the carcinogen.
Using a variety of microbiology and molecular biology methods, the researchers discovered that bacteria living in the mouse gut could convert BBN into BCPN. Like BBN, BCPN belongs to a class of compounds called nitrosamines.
However, the team found that, unlike BBN, BCPN concentrates in the urinary bladder and triggers tumor formation in a microbiome-dependent manner.
The researchers next studied over 500 isolated and cultured bacteria to identify the specific bacterial species involved in converting BBN to BCPN. "We found 12 species that can carry out this carcinogen biotransformation," said Boyao Zhang, co-first author of the study and former Ph.D. Student in the Zimmermann group.
"We sequenced them and were surprised to find that many of those species were skin-associated and found at relatively low abundance in the gut. We speculated that there might be some transient transfer of such bacteria from the skin to the gut as a consequence of the animals' grooming. But it was important to figure out whether these findings would also be true for humans."
Following these initial studies in mice, the scientists used human fecal samples to show that human gut bacteria can also convert BBN to BCPN. As a proof of concept, they showed that if human stool was transplanted into the intestine of a mouse that had no gut microbiome of its own, they could also convert BBN to BCPN.
However, the researchers also observed large individual differences in the ability of the human gut microbiome to metabolize BBN, as well as in the bacterial species involved in the biotransformation.
"We think this lays the foundation for further research to see whether a person's gut microbiome represents a predisposition for chemically induced carcinogenesis and could hence be used to predict the individual risk and potentially prevent cancer development," said Zimmermann.
"This difference in interindividual microbiota could explain why some people, despite being exposed to potential carcinogens, do not develop cancers while others do," Terzić added.
Do these findings mean antibiotics can universally prevent cancer? No, of course not, says Zimmermann.
"This calls for more studies, including some that we are doing currently, to understand how the microbiome influences the metabolism of different types of carcinogens. It is also important to remember that cancer is a multifactorial disease—there is rarely a single cause."
More information: Michael Zimmermann, Gut microbiota carcinogen metabolism causes distal tissue tumors, Nature (2024). DOI: 10.1038/s41586-024-07754-w. Www.Nature.Com/articles/s41586-024-07754-w
Citation: Gut microbes implicated in bladder cancer (2024, July 31) retrieved 6 August 2024 from https://medicalxpress.Com/news/2024-07-gut-microbes-implicated-bladder-cancer.Html
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FOUR IN FIVE AGED 55 AND OVER ARE UNAWARE OF BLADDER CANCER AND ITS SYMPTOMS DESPITE BEING MOST AT RISK
4th July 2024: In a revealing survey commissioned and funded by Merck Healthcare, it emerged that a staggering four in five (82%) people aged 55 and older are largely uninformed about bladder cancer, despite being among those most at risk. Age is a significant risk factor for the disease, second only to smoking, with over 70% of bladder cancer cases found in individuals over 65.
The survey – which is the largest bladder cancer awareness survey conducted in the UK and Ireland - highlighted a stark contrast in awareness levels across age groups, with older adults being far less aware than their younger counterparts aged 18-34 (60%) and 35-54 (70%). This lack of awareness spreads across all groups in the UK and Ireland, with more than seven out of ten (71%) people admitting they know little to nothing about bladder cancer. These insights underscore a critical need for better education and awareness across all age groups, particularly those most vulnerable.
The survey, commissioned and funded by Merck, with advice from the patient groups World Bladder Cancer Patient Coalition and Fight Bladder Cancer, asked more than 4,000 people in the UK and Ireland what they know about the disease and its symptoms as part of 'Bladder Cancer Awareness Month' which takes place throughout May.
Cause for concern
The results are likely to cause alarm among experts after bladder cancer moved up from the 10th to the 9th most diagnosed cancer worldwide and the 5th most common in Europe.1,2 It is known as one of the more challenging cancers to experience and to treat, with one of the highest recurrence rates in cancer of up to 80%3 and a mortality rate of up to 50%3 for invasive bladder cancer. Both incidence and mortality rates are also increasing; more than 10,000 people in the UK are diagnosed with the disease each year, with 15 related deaths every day (2017-2019).4
At risk occupations
Certain occupations working with or near cancer-causing chemicals have been associated with a higher risk of bladder cancer, for example:
Despite the increased risks, those working in 'high risk' occupations as hairdressers, plumbers, and painters are much less likely to contact their GP for bladder cancer symptoms, according to the survey, revealing a concerning risk that could lead to the quiet progression of this common yet often overlooked cancer.
The survey found that one in three (37%) people in higher risk industries would not seek medical advice for brown or red urine, a key symptom which could indicate the presence of blood, compared to 17% of the general population. Worryingly, almost two in three (68%) people in higher risk industries would not seek medical advice for a lump in their pelvic area compared to 41% of the general population.
"These findings are a wake-up call for the urgent need for increased public education on bladder cancer symptoms, particularly amongst those at higher risk due to their age or profession" said Dr Stuart Hill, Medical Director UK and Ireland at Merck Healthcare. "Merck has conducted research and provided education in bladder cancer for many years and we have seen first-hand not only the pain and suffering it causes patients and loved ones, but also how the area is affected by low public awareness. We hope that by sharing these powerful findings, more people might know the signs and symptoms and feel confident to seek help, particularly as early detection is crucial to successful treatment."
Barriers to seeking help
The survey also delved into why people might hesitate to seek medical treatment for bladder cancer, uncovering some telling reasons. A number of respondents 44% of said they were put off by the difficulty of getting a GP appointment. Close behind, 43% of those surveyed admitted they didn't believe their symptoms were serious enough to warrant medical attention. Additionally, 30% were discouraged by the prospect of long waiting times.
Also, stigma was indicated as a key barrier to people seeking help for worrying symptoms, with those in higher risk industries being significantly more likely to delay seeking advice due to embarrassment and fear of tests. Only half of people in higher risk industries are confident to talk to a GP about potential bladder cancer symptoms, with an even lower 10% feeling confident talking to their employer.
"Bladder cancer is recognised as the 'Cinderella of cancers' because it is less high profile compared with other cancers. It does not receive the same public support or advocation from important stakeholders," said Prof. Ananya Choudhury, Clinical Oncologist at the Christie NHS Foundation Trust. "It is important to start conversations with people with limited exposure to and awareness of bladder cancer wherever and whenever possible."
"The level of bladder cancer awareness in the UK is really low," said Dr Lydia Makaroff, Chief Executive of Fight Bladder Cancer. "We see so many people who are diagnosed with bladder cancer who've never heard of it, who feel that they're alone and feel like they don't know anyone else affected by the disease. The most significant barrier to raising awareness of bladder cancer is stigma, and we see many people who are very afraid about speaking about bladder cancer. If you notice any symptoms always speak to your GP, inform them about your occupation, and remember it is perfectly acceptable to insist on a blood test for bladder cancer or to seek a second opinion."
"Bladder Cancer awareness is low in the UK, and we need to try and change the stigma related around being diagnosed," said Emma-Jayne Kelly, Urology Clinical Nurse Specialist (CNS) at The Clatterbridge Cancer Centre NHS Foundation Trust. "It is not one of the more common cancers that people are aware of but is definitely on the rise. Encouragement to seek medical advice early if they have any symptoms of concern is key to better outcomes. Patients will always be fully supported throughout their journey to the highest level."
According to projections from The Health Foundation, cases of bladder cancer are expected to increase by around 50% in the UK over the next two decades, due to factors such as an ageing population and lifestyle changes. In response to this growing need to help people with bladder cancer manage the condition, Merck Healthcare have launched a patient app in collaboration with digital health company Huma, designed to support and empower those affected by bladder cancer in the UK through a digital-first approach to treatment and care.
Dr. Stuart Hill, highlights the significance of this initiative: "Our collaboration with Huma represents a pivotal step forward in addressing the challenges faced by bladder cancer patients. Being diagnosed with bladder cancer is the start of a long and complex journey and patients only have so much time with their doctors; by harnessing the power of digital technology, we aim to revolutionise the way patients are supported to understand, track and manage their condition, to ultimately improve treatment outcomes."
This app has been designed in collaboration with healthcare professionals in the NHS and leading patient organisations to offer patients reliable, personalised advice, treatment reminders, symptom tracking and information. It allows patients to track their symptoms and manage their medication, with the option to share this with their clinicians during appointments. Crucially, upon the advice from the NHS and patient groups, the app offers caregiver access for dual management of the patient's journey and to ensure maximum accessibility for patients and loved ones.
If you have experienced any of the symptoms listed below, or are worried about cancer symptoms, you should go and speak to your GP as soon as you can. If you require any assurance on contacting the GP you can speak to a pharmacist in the first instance.
For more information about bladder cancer and which occupations are higher-risk due to cancer-causing chemical exposure, please visit: https://fightbladdercancer.Co.Uk/get-help/signs-and-symptoms
[1] Action Bladder Cancer. The Facts About Bladder Cancer. Available at: https://actionbladdercanceruk.Org/the-facts-about-bladder-cancer/ [last accessed May 2024]Harling M, Schablon A, Schedlbauer G, et al. Bladder cancer among hairdressers: a meta- analysis(link is external). Occup Environ Med. 2010 May;67(5):351-8.
[2] Takkouche B, Regueira-Méndez C, Montes-Martínez A. Risk of cancer among hairdressers and related workers: a meta-analysis(link is external). Int J Epidemiol. 2009 Dec;38(6):1512-31.
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