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Genetic Variants Predict Recurrence of Bladder Cancer, Patient Survival
April 21, 2009Scientists at The University of Texas M. D. Anderson Cancer Center have discovered genetic variations in the inflammation pathway that reduce the likelihood of recurrence and increase survival of patients with non-muscle invasive bladder cancer (NMIBC) who are treated with mainstream therapy.
Patients with risk-reducing genotypes were 84 percent less likely to have their disease recur after treatment with Bacillus Calmette-Guerin (BCG), the prevailing immunotherapy to prevent high-risk NMIBC patients from developing recurrence. The recurrence-free median survival time among these patients was 96.7 months compared with 47 months among those with the more typical genotype, the team reported at the 100th Annual Meeting of the American Association for Cancer Research.
"The future purpose of this kind of study is personalized cancer therapy," said senior author Xifeng Wu, M.D., Ph.D., a 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."
Currently, the primary treatment for NMIBC is transurethral resection - surgical removal of the tumor tissues from bladder - combined with chemotherapy or immunotherapy such as BCG injection. Overall, the recurrence rate is around 50 percent over four years.
In this study of 596 patients at M. D. Anderson, 46 percent of those who had a common genotype of the inducible nitric oxide synthase (iNOS) gene experienced a recurrence after receiving maintenance BCG therapy. Only 22 percent of patients with the variant-containing genotypes had a recurrence with the same treatment. The results suggest that BCG may be more effective when administered to individuals with genotypes containing the variant allele of the iNOS gene.
"We aimed to determine why some patients respond to BCG and others don't," said lead author Hushan Yang, Ph.D., a postdoctoral fellow in the Department of Epidemiology at M. D. Anderson.
Yang and his colleagues evaluated 59 single nucleotide polymorphisms (SNPs) in 35 major inflammation genes. Using a combined analysis, they stratified patients into multiple risk groups. Those patients in the high-risk group were found to have a median survival time of only 13.5 months, while those in the low-risk group were recurrence free for more than 96.7 months.
"Once validated, the next step will be to create a risk prediction model," said Wu. "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."
In addition to Yang and Wu, other authors on the study included Colin P. Dinney, M.D., H.B. Grossman, M.D. and Ashish Kamat, M.D., of the Department of Urology at M. D. Anderson; and Jian Gu, Ph.D., of the Department of Epidemiology at M. D. Anderson.
The project was funded by grants from National Cancer Institute.
The University of Texas M. D. Anderson Cancer Center
Currently, the primary treatment for NMIBC is transurethral resection - surgical removal of the tumor tissues from bladder - combined with chemotherapy or immunotherapy such as BCG injection. Overall, the recurrence rate is around 50 percent over four years.
In this study of 596 patients at M. D. Anderson, 46 percent of those who had a common genotype of the inducible nitric oxide synthase (iNOS) gene experienced a recurrence after receiving maintenance BCG therapy. Only 22 percent of patients with the variant-containing genotypes had a recurrence with the same treatment. The results suggest that BCG may be more effective when administered to individuals with genotypes containing the variant allele of the iNOS gene.
"We aimed to determine why some patients respond to BCG and others don't," said lead author Hushan Yang, Ph.D., a postdoctoral fellow in the Department of Epidemiology at M. D. Anderson.
Yang and his colleagues evaluated 59 single nucleotide polymorphisms (SNPs) in 35 major inflammation genes. Using a combined analysis, they stratified patients into multiple risk groups. Those patients in the high-risk group were found to have a median survival time of only 13.5 months, while those in the low-risk group were recurrence free for more than 96.7 months.
"Once validated, the next step will be to create a risk prediction model," said Wu. "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."
In addition to Yang and Wu, other authors on the study included Colin P. Dinney, M.D., H.B. Grossman, M.D. and Ashish Kamat, M.D., of the Department of Urology at M. D. Anderson; and Jian Gu, Ph.D., of the Department of Epidemiology at M. D. Anderson.
The project was funded by grants from National Cancer Institute.
The University of Texas M. D. Anderson Cancer Center
Epidemiology Current Events and Epidemiology News RSSCigarettes Harbor Many Bacteria Harmful to Human Health
Cigarettes are "widely contaminated" with bacteria, including some known to cause disease in people, concludes a new international study conducted by a University of Maryland environmental health researcher and microbial ecologists at the Ecole Centrale de Lyon in France.
Preventing H1N1 spread to health care workers: Dilemma, debate and confusion
A commentary in the December issue of The Lancet Infectious Diseases brings to light the gaps in knowledge on the transmission of a common pathogen - the influenza virus - and its impact on decisions about how best to protect health care workers.
Research calls for better assessment of tests for tuberculosis, HIV/AIDS and malaria
A rapid and accurate diagnosis is the first step towards treatment in the fight against infectious disease.
Pilot study relates phthalate exposure to less-masculine play by boys
A study of 145 preschool children reports, for the first time, that when the concentrations of two common phthalates in mothers' prenatal urine are elevated their sons are less likely to play with male-typical toys and games, such as trucks and play fighting.
Drugs to treat anemia in cancer patients linked to thromboembolism
Medications frequently given to cancer patients to reduce their risk of anemia are associated with an increased risk of deep vein thrombosis or pulmonary embolism, according to new research led by Dawn Hershman, M.D, M.S., co-director of the breast cancer program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center.
A pain in the neck
The world record for fastest text message typing is held by a 21-year old college student from Utah, but his dexterous digits could mean serious injury later on.
Researchers mobilizing global resources to test new treatments for severe H1N1 infection
An important, ground-breaking initiative is unfolding in the global critical care community in response to the H1N1 pandemic.
People with less education could be more susceptible to the flu
People who did not earn a high school diploma could be more likely to get H1N1 and the vaccine might be less effective in them compared to those who earned a diploma, new research shows.
Expectant moms, babies subjects of new Singapore study to prevent obesity and diabetes in adults
Three Singapore biomedical institutions have launched a major, long-term study of pregnant mothers and their fetuses as well as infant children to determine just how profoundly environmental factors early in life influence the onset of diseases such as obesity and diabetes in later years.
Local health investigation sheds light on gastroschisis birth defect
Results of an investigation conducted by University of Nevada, Reno researchers, public health officials and area physicians published this week in the Archives of Pediatrics & Adolescent Medicine, indicate that Washoe County experienced a cluster of a particular birth defect, gastroschisis, during the period April 2007 - April 2008.
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