A Sexually Active 29-Year-Old Man With Urinary Straining

Liana Meffert; Paul Gellhaus, MD


March 20, 2023

Genetic counseling was recommended for this patient because of his significant family history of bladder cancer. Although many genetic factors and molecular alterations have been studied for their possible contribution to bladder cancer, no single mutation has been identified as a primary cause. Because exposures play a well-established role in the development of bladder cancer, genes that have been most closely scrutinized in genome-wide association studies include those involved in chemical carcinogenesis, DNA repair, and cell cycle pathways.[8] Two leading candidates include gene polymorphisms for the carcinogen-detoxification genes NAT2 and GSTM1. Mutations in these genes can modify an individual's susceptibility to carcinogens, such as those from tobacco use.[9]

Even studies that do identify genes associated with increased susceptibility to bladder cancer acknowledge that this multifactorial disease requires increasingly large sample sizes to control for myriad variables. For now, it remains most accurate to say that bladder cancer results from complex gene-environment interactions that are probably influenced by genetic susceptibility.

Bladder cancer is more common in men than in women worldwide, with an age-standardized incidence rate of 10.1 per 100,000 for males and 2.5 per 100,000 for females. It is estimated that 3% of all new cancer diagnoses and 2.1% of cancer deaths can be attributed to bladder cancer, which is ranked 10th worldwide in absolute incidence of cancers.[10]

In Western countries, cigarette smoking is a well-established risk factor; it contributes to approximately 50% of cases in men and 35% in women. Of note, the rise and fall of tobacco consumption in the developed world has partially mirrored the incidence of urothelial bladder cancer.[11] Occupational exposure to carcinogens also contributes to the development of urothelial carcinoma.[12]

Whereas urothelial bladder cancer is the predominant histopathologic presentation in the Western world, squamous cell carcinoma is dominant in regions where Schistosoma haematobium, a parasitic urinary blood fluke, is endemic. The contribution of S haematobium to bladder cancer is second only to that of tobacco. Another established risk factor is age: More than 90% of the time, bladder cancer presents in persons aged 55 years or older.[12]

Although tobacco consumption has been widely reduced in the developing world, an aging population — for whom the estimated life span is now well beyond 55 years — makes it unlikely that the incidence of bladder cancer will decrease any time soon.[13] Our ability to screen for, diagnose, and treat this do-not-miss diagnosis remains vital.


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