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Genetic Variants Predict Bladder Cancer Recurrence, Survival
Cancer Newsline - July 2009
SNPs Play Roles After Standard Treatment
Variations in genes that modulate inflammation in the body can influence survival rates and recurrence in patients with non-muscle invasive bladder cancer (NMIBC) who are treated with one of the most common therapies for this disease.
Scientists from M. D. Anderson reported their findings at the annual meeting of the American Association for Cancer Research in March.
Significance of results
NMIBC is the most common type of bladder cancer. Although initially the disease generally can be treated successfully, up to 70% of patients experience a recurrence.
The primary treatment for NMIBC is transurethral resection (surgical removal of the tumor tissues from the bladder) combined with chemotherapy or immunotherapy, usually with Bacillus Calmette-Guerin (BCG).
The anti-tumor mechanism of BCG treatment depends largely on immune and inflammatory responses, so researchers wanted to assess the effects of inflammation-related genetic variations on outcome of NMIBC patients receiving BCG therapy.
"We aimed to determine why some patients respond to BCG and others don't," says lead author Hushan Yang, Ph.D., a postdoctoral fellow in the Department of Epidemiology.
Research methods
In this study of 596 patients at M. D. Anderson, Yang and his colleagues evaluated 59 gene variations called single nucleotide polymorphisms (SNPs) in 35 major inflammation genes to try to find the roles they might play in preventing or facilitating recurrence.
Primary results
Several SNPs were found to be significantly associated with recurrence after BCG treatment.
Among them, a variation of the inducible nitric oxide synthase (iNOS) gene was associated with a significantly reduced risk of recurrence. Patients with this variation were 84% less likely to have their disease recur after treatment with Bacillus Calmette-Guerin (BCG). The recurrence-free median survival time among these patients was almost 97 months compared with 47 months among those with the more typical genotype.
Additional results
These effects were found only in patients who received BCG treatment. This indicates these SNPs may predict BCG therapy response but not prognosis of bladder cancer in general.
Researchers identified subgroups of patients with different recurrence risk levels based on different combinations of inflammation SNP genotypes.
The low-risk patient group had a median survival time of more than 96 months, while the high-risk group’s was close to 14 months.
What’s next?
"The future purpose of this kind of study is personalized cancer therapy," says senior author Xifeng Wu, M.D., Ph.D., professor in the Department of Epidemiology at M. D. Anderson. "This genetic information is an essential step toward constructing a blueprint that will determine treatment response and follow-up strategy."
"Once validated, the next step will be to create a risk prediction model," Wu says. "Combining the information we have with other aspects such as clinical, epidemiological and behavioral variables, as well as tumor characteristics, patient characteristics and other genetic information will allow treating physicians to know whether their patient is likely to respond to therapy or experience a recurrence."
Adapted by Dawn Dorsey from anM. D. Anderson news release.
M. D. Anderson resources:
Other resources:
All About Bladder Cancer (American Cancer Society)
Bladder Cancer (National Cancer Institute)