Observed genes

Polygenic score

Influential genes: CASC11,TACC3

CASC11 can play crucial roles in the regulation of gene expression. Studies suggest that its overexpression may promote tumor progression, including in bladder cancer.

TACC3 is crucial in cell division during mitosis. Mutations or overexpression of TACC3 have been found in various cancers, including bladder cancer.

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Summary 

Bladder cancer is the 10th most common cancer worldwide. There are many risk factors, with smoking being the most significant modifiable one. Bladder cancer has an excellent prognosis when diagnosed in its early stages. 

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Overview

Bladder cancer is the 10th most common cancer worldwide. There are many risk factors, with smoking being the most significant modifiable one. The other risk factors include being male, old age, exposure to carcinogens, consumption of alcohol and red meat, obesity, infections, etc. Bladder cancer typically presents with blood in the urine. Other symptoms like frequency of and pain during urination, or lower back pain, can also be present. In some cases, it can be asymptomatic. There are several examination methods available that can help with diagnosing bladder cancer. For example, cystoscopy, urinalysis, CT urogram, etc. The choice of treatment depends on several factors. You might prevent bladder cancer development by following some simple instructions: quit smoking, drink plenty of fluid, avoid carcinogens, alcohol, red meat, and consume a variety of fresh fruit and vegetables. The prognosis of bladder cancer is excellent when diagnosed at early stages. 

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Prevalence & Risk factors

Bladder cancer is the 10th most common cancer worldwide. In 2020, there were more than 500 thousand new cases. Greece has the highest prevalence of bladder cancer. It is mainly attributable to the high percentage of the smoking population. [1]

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Several risk factors contribute to the development of the disease. These include:

• Gender. Bladder cancer occurs four times more commonly in men than women. [2]
• Age. Bladder cancer predominantly affects older individuals. It mainly develops in people around 65-70 years of age. [2]
• Smoking. Smoking is the most significant modifiable risk factor for developing this type of cancer. It increases the risk by 3-4 times. [3]
• Occupational exposure. The second most important preventable risk factor is occupational exposure to carcinogens like aromatic amines, polycyclic aromatic hydrocarbons, and chlorinated hydrocarbons. These chemicals are used in the manufacture of dyes, rubber, leather, textiles, and paint products. It is estimated that 18% of bladder cancer cases are attributable to occupational exposure. [4]
• Environmental exposure. A naturally occurring heavy metal - arsenic, was also found to increase the risk of bladder cancer. However, most people aren't exposed to it in large amounts. [5]
• Alcohol. Alcohol was found to increase the risk of this cancer slightly. [6]
• Red meat. Recent studies have proved that consuming red and processed meat increases bladder cancer risk by around 15%. [7] 
• Obesity. Obesity was found to increase the risk of bladder cancer by 10%. [8] 
• Pathogens. A tropical parasite - protozoan schistosomiasis, infects people through freshwater exposure. It is known for its association with bladder cancer. [9] 
• Chronic inflammation. Chronic or repeated cystitis (bladder inflammation) may increase the risk of bladder cancer. [10]
• Anti-cancer drugs. Certain medications used to treat cancer, like cyclophosphamide, have also been linked to developing this type of cancer. Also, radiation treatment to the pelvic region has been linked to it. [11]
• Not drinking enough water. It can keep carcinogens in the bladder for longer, causing more harm.
• Bladder anatomical congenital defects. 
• Hereditary and genetic factors. 

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Genetics 

Recent improvements in next-generation sequencing (NGS) technologies have largely helped scientists to understand the molecular processes happening during bladder cancer. Even though researchers suggest that positive family history among first-degree relatives might be a risk factor, results remain unclear. [16]

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From the genomics point of view, the mechanisms leading to bladder cancer are often related to oncogene activation and overexpression, mutations in tumor suppressor genes, loss of gene repair function, various nucleotide abnormalities, or defects in the signaling pathways. [17]

Genetic changes (mutations) in certain genes, e.g. FGFR3, RB1, HRAS, TP53, or TSC1, are considered to be involved in tumor formation in the urinary bladder; these genes are important in cell division regulation. 

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Expression of the HER2 gene was examined in 354 patients and it was observed that in more than 32% of cases, the gene was highly expressed. Gene expression means that the genetic information (DNA) is copied to a molecule of mRNA (transcription, in the nucleus); these mRNA molecules are later transported to the cytoplasm, where the protein synthesis takes place (translation). 

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The cancer genome atlas (TCGA) studied genetic information (DNA) from 131 patients with muscle-invasive bladder cancer (MIBC), resulting in the identification of 32 affected genes. Furthermore, research of another TCGA group (composed of 412 MIBC patients) pointed out 58 mutated genes. Analysis of DNA methylation and gene expression was also performed, finding that 158 genes were epigenetically silenced (meaning gene expression is affected but there is no change in the DNA sequence). [17,18]

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In Macromo, polygenic risk scores are used to determine the genetic risk. The polygenic risk score (PRS) is an estimate of the probability that an individual carries a given trait based on genetics, without considering environmental factors. Variants across their genome are summed and weighted according to their effect on the disease or trait.

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Signs & Symptoms

Bladder cancer usually presents with nonspecific symptoms, but sometimes it can be asymptomatic. Other less severe medical conditions can present with the same symptoms. 

Usually, the first sign at a presentation is hematuria - blood in the urine. In some cases, you can see it with the naked eye (gross hematuria). In other cases, it can be found only after a urine lab test (microscopic hematuria). [12]

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Other symptoms include:

• Pain or burning sensation during urination 
• Urinary frequency (using the bathroom too often) 
• Feeling the urge to urinate several times through the night
• Feeling the need to urinate but not being able to pass the urine
• Lower back pain

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If cancer has spread to distant organs (metastasized), you can experience other symptoms depending on the affected organs. 

If you experience any of the symptoms, consult with your GP. It is very likely caused by benign conditions like cystitis (bladder inflammation), but they should be treated anyway. 

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Diagnosis

Your doctor can perform several tests to detect bladder cancer and learn more about it. However, not everyone will need all of the following examinations. [13] These include: 

• Analysis of urine. A sample of urine is diagnosed under a microscope for the presence of cancer cells. 
• Cystoscopy. Your doctor will use a cystoscope - a special thin device with a lens inserted through the urethra, to examine and visualize your bladder from the inside. 
• Biopsy. During cystoscopy, a piece of tissue can be removed to be examined under the microscope. Sometimes this procedure is called transurethral resection of bladder tumor (TURBT) and can be used to treat cancer.
• CT urogram. It's a procedure performed using contrast dye to visualize the urinary tracts after a series of images by computer tomography. The contrast can be injected into the vein or directly into the urethra. 
• Other tests include biomarker testing and genetic counseling. 

Additional imaging tests can be performed to determine if it has spread to distant organs. These include a CT scan, MRI, PET-CT, and ultrasound. 

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Therapy 

Several treatment options for bladder cancer are available. The method of choice depends on several factors. The stage of cancer, grade (how aggressive it is), type, and the patient's wishes contribute to selecting the right treatment option. [13] 

The treatment options include: 

• Surgery. It can be a less aggressive surgery like the transurethral resection of bladder tumor (TURBT) or a complete removal of the bladder - cystectomy. 
• Intravesical chemotherapy. If cancer is confined to the lining of the bladder, chemotherapy (special anti-cancer treatment) can be injected directly into the bladder. 
• Systemic chemotherapy. Chemotherapy for the whole body can be used to make the tumor smaller before surgery or instead of it if the cancer is not operable. 
• Radiotherapy. Radiation can be used to treat cancer when surgery is not possible. 
• Immunotherapy. It triggers an immune response and makes your immune cells destroy cancer. 
• Targeted therapy. This type of treatment is preferred in advanced cases when other options have failed. 

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Prevention

You might be able to prevent bladder cancer by making some lifestyle modifications. 

• Approximately half of bladder cancer cases are linked to smoking, including cigarettes, pipes, cigars, etc.  If you smoke, talk to your doctor or specialist to help you quit. [3]
• Avoid exposure to carcinogens. You can be exposed to harmful chemicals if you work in manufacturing dyes, rubber, leather, textiles, paint products, etc. Make sure to follow all the safety rules and use protective equipment while working. [4]
• Eat a variety of fresh fruit and vegetables. Several studies suggest that it can lower cancer risk due to the high amount of antioxidants. [14]
• Drink lots of water. 
• Limit consumption of alcohol. [6]
• Limit consumption of red meat. [7]
• Lose extra weight. Obesity is linked to higher risks of bladder cancer, so losing excess weight can help you prevent it. [8]
• Genetic testing. If you have a strong family history of bladder cancer, it might be a good idea to undergo genetic testing to be aware of your risks.

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Prognosis 

The 5-year survival rate means the percentage of people who survived for five years after the diagnosis. In general, the 5-year survival rate of bladder cancer is 77%. However, if it was diagnosed in the early stages, the 5-year survival rate is estimated to be much higher, 96%. [15] 

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Recommendations

• Quit smoking if you are an active smoker. If you are not an active smoker, avoid passive smoking too.
• Avoid exposure to carcinogens. 
• Eat a variety of fresh fruit and vegetables. 
• Drink lots of water. 
• Limit consumption of alcohol.
• Limit consumption of red meat.
• If you are overweight, try to reduce your weight. A nutritionist can also assist you with this process.
• Visit your GP if you have any symptoms of bladder cancer. 

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