Wednesday, July 16, 2003

By Michael Woods, Post-Gazette National Bureau
 

WASHINGTON -- Millions of men carry genes that cause a positive result on the blood test for prostate cancer even though they are cancer-free, contributing to tens of thousands of unnecessary biopsies each year at an average cost of $1,400, scientists reported yesterday.

It was the first study to show that individual genetic variations can cause "false positives" in reaction to the widely used prostate specific antigen test.

If all men over 50 had an annual PSA test, as recommended by health groups, the number of false-positives could result in $12 billion in unnecessary biopsies.

Testing for the newly discovered gene variants is quick and inexpensive and could become a part of the PSA screening regimen, greatly reducing the number of false positives, said the study's chief author.

"We've known that age, race and disease can influence PSA levels," said Dr. Scott D. Cramer of Wake Forest University in Winston-Salem, N.C. "Now, we can add genetics to the list." Cramer headed the study, which was published in the Journal of the National Cancer Institute.

Cramer estimated that 29 million men may have the genes that produce levels of PSA about 30 per cent higher than average. PSA is a protein manufactured by prostate cancer cells and released into the blood. The PSA test measures those levels.

PSA levels are higher in African American men, older men and men with a common non-cancerous enlargement of the prostate.

Many doctors now recommend a biopsy when PSA levels are higher than 4 nanograms per millilter. But there is controversy about the exact cut-off point that separates "normal" from "abnormal" PSA levels. Some doctors use 3.0 or 2.5 as the upper limits of normal.

An editorial in the Journal of the National Cancer Institute commenting on the PSA controversy took the tile, "The More We Know, the Less We Understand."

"Only one man in four with a PSA level greater than 4.0 is found to have prostate cancer on biopsy," it noted. "And about one-third of prostate cancers are detected in men with a normal PSA level."

Cramer's group analyzed blood from 409 healthy white men, using a genetic technique that identified three variations in a gene that controls PSA levels. Their analysis suggested that if a man has one of the variations, he has all three. The variations occurred in about 20 per cent of the study group.

Men could receive both a standard PSA test and a test for the genetic variations that raise PSA. Doctors would use a higher cut-off point for defining normal PSA in men with the gene variants, avoiding some unnecessary biopsies.

"Because of the huge importance of accurately diagnosing prostate cancer, we need to find the best ways to use PSA to determine who has cancer and who doesn't" Cramer said.

Prostate cancer is the most common form of cancer in men, aside from skin cancer, and is second only to lung cancer as the leading cause of cancer death in men. About 200,000 new cases and 32,000 deaths occur each year.

(Michael Woods can be reached at mwoods@nationalpress.com or 1-202-662-7072. .)