A urine test for genetic flaws may help detect bladder cancer in its deadly invasive form and also may pave the way for similar tests for even more common types of cancer, researchers said.
The prospect of simple, urine screening for bladder cancer stems from the discovery of the first genetic defect to be found in a large proportion of such tumors.Bladder cancer is the fifth most common type of cancer in the United States, with more than 50,000 new cases and 9,500 deaths expected in 1991.
When detected at an early, superficial stage, the five-year survival rate is nearly 90 percent, the American Cancer Society said Thursday. But if the tumor has invaded the bladder wall or other tissues, the five-year survival rate falls to about 44 percent even if the patient has undergone surgery to remove the bladder, radiation or chemotherapy, the society said.
A team headed by Dr. Bert Vogelstein of Johns Hopkins School of Medicine in Baltimore said it found 11 of 18 - or 61 percent - of invasive bladder cancer tumors had mutations in a gene on the so-called long arm of chromosome 17. Every person has 23 pairs of chromosomes containing 100,000 genes that bear the blueprints for everything from hair color to disease risk.
The gene, called p53, normally is thought to produce a protein that acts as a brake on cell growth. But when p53 is damaged, that brake is lifted and runaway, cancrous growth procedes unchecked. Defects in p53 previously have been found in about half of breast, colon, lung and liver tumors.
Not content to simply identify the p53 defect in bladder tumors removed from the body, Vogelstein's team went on to develop a way of using the genetic clue to detect cancer cells shed from tumors and passed into patients' urine.
Using a sophisticated technique that amplifies genetic material, researchers found that urine sediments collected from three bladder cancer patients before tumor-removal surgery bore the same p53 defects as their tumors.
Doctors possibly could screen people at high risk for bladder for the presence of p53 mutations in their urine, Vogelstein. People known to be at increased risk for the malignancy include smokers, those who work with dye, rubber or leather and those who live in urban areas.
It is not known if the p53 mutations - which were found only in cancerous bladder cells, not healthy cells - occur early or late in the chain of genetic damage thought to lead to cancer. Researchers are now looking at superficial bladder cancer tumor to see if they contain defects similar to invasive tumors.
In addition, a urine test for p53 defects could help doctors keep a closer watch on possible tumor recurrence in bladder cancer patients who have undergone surgery in which part of their bladder is spared.