Polymorphisms in the promoter region of the prostate-specific antigen gene may contribute to individual variations in PSA levels, according to researchers in North Carolina.
The results may help researchers develop a more accurate diagnostics product to detect a man’s risk of developing prostate cancer.
“The results of the current study suggest that genotyping SNPs in the far upstream region of the PSA gene may improve the sensitivity of PSA testing for prostate cancer,” the researchers wrote in the July 16 issue of the Journal of the National Cancer Institute.
Other scientists had previously linked a SNP in the PSA gene promoter to increased serum PSA levels in healthy men. However, this SNP was eventually found not to influence PSA levels in two different groups of healthy men.
In the new study, Scott Cramer, of the Wake Forest University School of Medicine in Winston-Salem, NC, and colleagues, looked at PSA genes from 409 healthy white men at risk for lung disease. The team identified three SNPs — -4643A/G, -5412T/C, and -5429T/G — in the promoter region of the PSA gene that influences serum PSA levels.
Cramer’s team suggested that “future studies should examine whether these polymorphisms can be used to help to determine PSA cutoff values for further testing by prostate needle biopsy.” According to the researchers, PSA testing “has been limited by its lack of sensitivity and specificity.” For example, men with a serum PSA level greater than 4 ng/mL are “typically” referred for a prostate needle biopsy. “However,” the team said, “factors such as benign prostate disease, age, and race contribute to individual variations in PSA level, making it difficult to determine which patients should undergo further testing.”
The current findings suggest that the cutoff value for a man with a PSA promoter genotype associated with reduced serum PSA levels may be lower than that for a man with a genotype that is associated with elevated serum PSA levels.
“Our results suggest that the SNPs in the far upstream enhancer region of the PSA gene may be good candidates for incorporation into a genetic model for prostate cancer risk,” the authors wrote.
However, writing in an accompanying editorial, Ian Thompson, of the University of Texas Health Science Center at San Antonio, and colleagues caution that “we cannot be certain whether these polymorphisms directly affect PSA levels in men or whether they increase the risk of prostate cancer and thereby (indirectly) increase PSA levels. Clearly the role of PSA in prostate cancer detection needs further exploration,” the editorialists wrote.
“Although PSA has had a profound effect on the identification of prostate cancer, this study demonstrates the need to constantly refine and improve this important diagnostic tool and to explore other diagnostic modalities,” Thompson wrote.
Prostate cancer is the most common cancer in American men, other than skin cancer.