A specific gene variation in the prostate stem cell antigen (PSCA) gene causes a 30% to 40% higher risk for urinary bladder cancer, according to a scientific team led by The University of Texas M. D. Anderson Cancer Center. They say that the rs2294008 variant was associated consistently with the disease and was found to be the only common missense genetic variation in the PSCA gene region.
PSCA is overexpressed in prostate cancer, and the level of PSCA increases with tumor grade and stage. While PSCA’s involvement in bladder cancer was suggested previously, this is the first time it has been linked definitively, according to the M. D. Anderson team. The findings were reported yesterday in the advance online publication of Nature Genetics in a paper titled, “Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer”.
“With this research, we were able to find a novel specific gene and a functional variation that are independent of the previous suspects,” notes Xifeng Wu, M.D., Ph.D., professor in M. D. Anderson's department of epidemiology, division of cancer prevention and population sciences. “The neighboring genomic region has been identified previously as a possible problem for breast, prostate, colorectal, and bladder cancer, but we didn't know why.”
The study began with a genome-wide evaluation of 969 people with bladder cancer and 954 healthy people. To validate their findings, researchers evaluated patients from three additional U.S. and nine European groups, for a total of 6,667 people with bladder cancer and 39,590 healthy people.
rs2294008 was the only genetic variation in the PSCA region linked with bladder cancer across all studies, the investigators report. Low levels of PSCA were found in the bladders of healthy people, but it was overproduced in the majority of patients with bladder cancer. Previous reports suggest that measurement of PSCA in urine may be a simple and accurate marker to help diagnose bladder cancer, though, the cellular function of PSCA in prostate cancer is not clear.
Next the group plans to fully analyze data jointly with other participating centers. “When we've identified all the genes that are linked to bladder cancer, we plan to develop a web-based tool so physicians can calculate accurately and easily a patient's risk of getting the disease,” says Dr. Wu. Her team is also working with a hospital in Spain to compare findings of the study to clinical outcomes.