Bladder cancer was the 10th most common cancer type worldwide in 2020. Every year, about 600 000 people are diagnosed with bladder cancer worldwide, and more than 200 000 people die from this disease. In Africa, 33 000 new cases of bladder cancer and 19 000 deaths from the disease occurred in 2020, and this burden is predicted to nearly double by 2040.
In most countries, urothelial carcinoma accounts for 90–95% of bladder cancers, and a large proportion of the burden is attributed to tobacco smoking, exposure to occupational carcinogens, and arsenic in drinking-water. In contrast, in Africa, most bladder cancers are of a different histological subtype: squamous cell carcinomas associated with chronic bladder irritation. Up to 85% of squamous cell carcinomas of the bladder in Africa are associated with chronic infection with Schistosoma haematobium, a parasitic blood fluke that is found in rivers and freshwater lakes. Communities living near the Rift Valley lakes and rivers, and people who work in paddy fields, for example near Lake Malawi, are particularly affected. Humans are a host for the S. haematobium fluke, and freshwater snails are intermediate hosts; thus, contact with affected African rivers and freshwater lakes results in a high population prevalence of infection and high incidence rates of bladder cancer. In Malawi, bladder cancer is the sixth most common cause of cancer death. However, there have been no individual-level studies of risk factors, other than S. haematobium, in this setting. Putative risk factors include other infections and lifestyle factors such as tobacco smoking and alcohol consumption. Although S. haematobium is a recognized bladder carcinogen, the mechanism by which carcinogenesis occurs is still unclear, and it may have complex associations with other risk factors for bladder cancer, such as tobacco smoking, exposure to occupational carcinogens, and co-infections.
Bladder cancer is a highly recurrent disease and is one of the most challenging and expensive cancers to diagnose and treat. Currently, its diagnosis relies on cystoscopy of individuals with symptoms (haematuria, dysuria). Cystoscopy is an invasive and expensive procedure that is not widely available in low-resource settings.
The aims of the BEED study are:
The third aim builds on previous work at IARC. Specifically, IARC scientists have developed an inexpensive urinary biomarker for the early detection of urothelial carcinomas of the bladder. This assay detects the presence of specific mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in urine samples. These TERT promoter mutations (TERTpm), which are frequently found in several tumour types, are present at a high frequency (60–85%) in all stages and grades of urothelial carcinomas and are the most frequent genetic alterations. Previous work by IARC scientists showed that urinary TERTpm has excellent diagnostic accuracy for the detection of urothelial cancer and that these mutations could also be detected in urine samples of asymptomatic individuals years before primary diagnosis of bladder cancer, with high specificity. However, urinary TERTpm has never been studied in sub-Saharan Africa, or in any settings where Schistosoma-associated squamous cell carcinomas of the bladder are common.
For more information about IARC’s work on TERTpm, watch the video below.