Biologic markers help assess bladder cancer risk

Key Points

Providence, RI-A pattern of biologic markers derived from peripheral blood samples can assess a patient's risk for bladder cancer with significant accuracy and reliability, reports a team of investigators from Brown University's Warren Alpert School of Medicine, Providence, RI, and the Dartmouth Medical School, Lebanon, NH.

The team, led by Carmen Marsit, PhD, assistant professor of pathology and laboratory medicine at Brown University, measured a pattern of methylation, a chemical alteration to DNA that affects which genes are expressed in cells. They found that patients with a pattern of nine specific methylated CpG (cytosine-phosphate-guanine) loci were 5.2 times as likely to harbor bladder cancer as those who lacked the pattern (95% CI: 2.8-9.7).

This finding opens the possibility of a host of investigations, the first of which would be to develop a diagnostic or pre-diagnostic test for patients known to be at risk for the disease. These would be the elderly, heavy smokers, individuals exposed to a number of environmental factors such as certain hair dyes, and those with other known risk factors.

One of the advantages of such a test is that the methylation pattern can be identified in immune cells in peripheral blood. Another is that these loci are stable. Other biologic marker tests, such as those used in evaluating breast cancer and other malignancies, are based on RNA, which is more unstable and is susceptible to degradation during collection and processing, Dr. Marsit explained.

Finding the pattern in blood-derived immune cells raises yet another question with significant clinical implications. Does the methlyation pattern reflect exposure to environmental risk factors and precede the disease, or is it an immunologic response to undetected early-stage cancer?

"Either finding would be useful. If it is a response to the environment, then we could use it to design preventive strategies. If it is a response to disease, it may have the ability to assist diagnosis at a very early stage when the disease is more responsive to therapies," said Dr. Marsit.

"The other question I am asking is whether these findings can be used to evaluate or determine treatments for people diagnosed with the disease. Many of the therapies employed in bladder cancer engender inflammatory responses, so understanding what the specific immune response looks like might help determine which patients will respond best to which therapies," he added.

Advanced array technologies used

The researchers found the pattern by applying advanced bead array technologies to blood samples taken from 112 patients with bladder cancer and comparing them to a control group of 119 individuals without diagnosed cancer. This led the investigators to the pattern, which was then studied in a blinded fashion in a similar number of blood samples of patients with and without the disease.

Dr. Marsit noted that the technology and process might find other nucleotide methylation patterns in other cancers. This would be yet another avenue of investigation.

Results from the study were published online in the Journal of Clinical Oncology (Feb. 22, 2011).