Certain Genetic Variants May Help Identify Patients at Increased Risk of Bladder Cancer Recurrence
A new study by Andrew et al published in BJU International suggests that certain inherited DNA sequences may affect the prognosis of patients with bladder cancer. The findings may help physicians identify subgroups of patients with high-risk bladder cancer who should receive more frequent screenings and aggressive treatment and monitoring.
Although patients diagnosed with bladder cancer usually face a favorable prognosis, many experience recurrence after treatment. Because frequent, painful screenings are needed to identify recurrences, the ability to identify patients at high risk of recurrent cancer could help to improve quality of life for all bladder cancer patients.
"The genetic markers that we found could potentially be useful for individually tailoring surveillance and treatment of bladder cancer patients," said principal investigator Angeline S. Andrew, PhD, Assistant Professor of Community and Family Medicine and the Geisel School of Medicine at Dartmouth and a member of the Norris Cotton Cancer Center.
Study Details
Dr. Andrew and her colleagues analyzed the genes of 563 patients to identify genetic variants that modified time to bladder cancer recurrence and patient survival. The investigators isolated DNA from immune cells circulating in the blood, and then examined the genes involved in major biologic processes linked to cancer, including cell death, proliferation, DNA repair, hormone regulation, immune surveillance, and cellular metabolism.
After diagnosis, patients were followed over time to ascertain recurrence and survival status. Patients were followed for a median of 5.4 years, and half of patients experienced at least one recurrence.
Findings Could Guide Personalized Treatment
The team found that patients with a variant form of the aldehyde dehydrogenase 2 (ALDH2) gene, which encodes an enzyme involved in alcohol metabolism, were more likely to experience bladder cancer recurrence shortly after treatment (adjusted noninvasive hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.29–2.78). Time to recurrence was also shorter for patients who had a variation in the vascular cellular adhesion molecule 1 (VCAM1) gene and were treated with immunotherapy (P < .001). VCAM1 encodes a glycoprotein involved in the development of lymphoid tissues.
In addition, the researchers found that patients who had noninvasive tumors and a single variant allele in the DNA repair gene XRCC4 tended to live longer than patients who did not have the variant (adjusted HR = 0.53, 95% CI = 0.38–0.74).
"Our present data suggest novel associations between genetic variations (SNPs) and bladder cancer recurrence that merit future investigation," said Dr. Andrew. "Prognostic variations will help us to identify subgroups of bladder cancer patients at high risk of tumor recurrence and progression so that they can receive more personalized bladder cancer surveillance and treatment."
Dr. Andrew is the corresponding author for the BJU International article.
The study was funded in part by grants fro the National Cancer Institute, the National Institute of Environmental Health Sciences, the National Center for Research Resources, and the National Institute of General Medical Sciences.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
