Bladder cancer is characterized by the uncontrolled growth of abnormal cells in the bladder. While often linked to environmental factors like smoking, genetic predispositions also play a part. The development of this cancer involves genetic alterations that can be inherited or acquired during a person’s life.
Inherited Risk vs. Acquired Mutations
The genetic basis of bladder cancer falls into two categories: inherited and acquired mutations. Inherited (germline) mutations are present in every cell and are passed down through families. Although these mutations can increase a person’s lifetime risk of developing bladder cancer, they are not a common cause of the disease.
Acquired (somatic) mutations are far more common in bladder cancer. These genetic changes occur in bladder cells during a person’s life and are not passed on to their children. Such mutations often result from exposure to carcinogens, like those in tobacco smoke. These substances are filtered by the kidneys and accumulate in the urine, where they can damage the DNA of bladder cells.
The accumulation of acquired mutations can disrupt genes that control cell growth. Some mutations are random events, while others have external causes. Genes that prevent cells from dividing too quickly are known as tumor suppressor genes. When mutations turn these genes off, it can lead to the uncontrolled cell growth that characterizes cancer.
Key Genes and Hereditary Syndromes
Specific inherited genetic conditions increase the likelihood of developing bladder cancer. One is Lynch syndrome, associated with mutations in genes like MLH1 and MSH2. Another is Cowden syndrome, linked to mutations in the PTEN gene. Both syndromes increase the risk for various cancers, including bladder cancer.
More commonly, bladder cancer is associated with acquired mutations in genes within the tumor cells. Frequent mutations are found in FGFR3, TP53, PIK3CA, and RB1. The TP53 and RB1 genes are tumor suppressors that, when altered, lose their ability to control cell growth. The FGFR3 and PIK3CA genes are involved in signaling pathways that can drive cell proliferation when mutated.
Gene-environment interactions also contribute to bladder cancer. Some people inherit variations in genes like GSTM1 and NAT2, which help eliminate carcinogens from the body. These variations can make individuals more susceptible to substances like tobacco smoke. Additionally, mutations in the telomerase reverse transcriptase (TERT) gene are found in a high percentage of bladder cancers.
Role of Family History and Genetic Testing
A family history of bladder cancer can indicate an increased genetic risk. This is particularly true if multiple relatives on the same side of the family have had bladder cancer or if a relative was diagnosed at a young age. In these cases, a healthcare provider may recommend genetic counseling to assess for an inherited predisposition.
Genetic counseling involves a detailed review of personal and family medical history. A counselor helps the individual understand their potential risk and discusses the benefits and limitations of genetic testing. This procedure is not routine but is considered for those with a strong family history.
If genetic testing is pursued, it involves a blood or saliva sample to look for inherited mutations in cancer-risk genes. The results can clarify a person’s risk and inform medical management for them and their family. Inheriting a risk-associated gene mutation does not guarantee that a person will develop cancer.
Genetic Information in Prevention and Treatment
Understanding the genetic factors in bladder cancer has practical implications for prevention and treatment. For individuals with a known inherited risk from a hereditary syndrome, more vigilant screening may be recommended. This could involve earlier or more frequent monitoring to detect bladder cancer at an early, more treatable stage.
The genetic profile of the tumor is also important for treatment. Targeted therapy uses drugs designed to attack cancer cells with specific genetic mutations. For instance, medications that target the FGFR gene have been developed for bladder cancers with FGFR mutations.
A tumor’s genetic makeup can also help predict its response to treatments like immunotherapy. Certain genetic markers indicate if a tumor is likely to respond to these drugs, which help the body’s immune system attack cancer cells. This personalized approach to medicine, guided by genetic information, is a rapidly advancing area of bladder cancer care.