PURPOSE: Recent studies have identified genetic variants associated with increased serum prostate specific antigen concentrations and prostate cancer risk, raising the possibility of diagnostic bias. By correcting for the effects of these variants on prostate specific antigen, it may be possible to create a personalized prostate specific antigen cutoff to more accurately identify individuals for whom biopsy is recommended. Therefore, we determined how many men would continue to meet common biopsy criteria after genetic correction of their measured prostate specific antigen concentrations. MATERIALS AND METHODS: The genotypes of 4 single nucleotide polymorphisms previously associated with serum prostate specific antigen levels (rs2736098, rs10788160, rs11067228 and rs17632542) were determined in 964 healthy Caucasian volunteers without prostate cancer. Genetic correction of prostate specific antigen was performed by dividing an individual's prostate specific antigen value by his combined genetic risk. Analyses were used to compare the percentage of men who would meet commonly used biopsy thresholds (2.5 ng/ml or greater, or 4.0 ng/ml or greater) before and after genetic correction. RESULTS: Genetic correction of serum prostate specific antigen results was associated with a significantly decreased percentage of men meeting biopsy thresholds. Genetic correction could lead to a 15% or 20% relative reduction in the total number of biopsies using a biopsy threshold of 2.5 ng/ml or greater, or 4.0 ng/ml or greater, respectively. In addition, genetic correction could result in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses. CONCLUSIONS: Our results suggest that 4 single nucleotide polymorphisms can be used to adjust a man's measured prostate specific antigen concentration and potentially delay or prevent unnecessary prostate biopsies in Caucasian men.
PURPOSE: Recent studies have identified genetic variants associated with increased serum prostate specific antigen concentrations and prostate cancer risk, raising the possibility of diagnostic bias. By correcting for the effects of these variants on prostate specific antigen, it may be possible to create a personalized prostate specific antigen cutoff to more accurately identify individuals for whom biopsy is recommended. Therefore, we determined how many men would continue to meet common biopsy criteria after genetic correction of their measured prostate specific antigen concentrations. MATERIALS AND METHODS: The genotypes of 4 single nucleotide polymorphisms previously associated with serum prostate specific antigen levels (rs2736098, rs10788160, rs11067228 and rs17632542) were determined in 964 healthy Caucasian volunteers without prostate cancer. Genetic correction of prostate specific antigen was performed by dividing an individual's prostate specific antigen value by his combined genetic risk. Analyses were used to compare the percentage of men who would meet commonly used biopsy thresholds (2.5 ng/ml or greater, or 4.0 ng/ml or greater) before and after genetic correction. RESULTS: Genetic correction of serum prostate specific antigen results was associated with a significantly decreased percentage of men meeting biopsy thresholds. Genetic correction could lead to a 15% or 20% relative reduction in the total number of biopsies using a biopsy threshold of 2.5 ng/ml or greater, or 4.0 ng/ml or greater, respectively. In addition, genetic correction could result in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses. CONCLUSIONS: Our results suggest that 4 single nucleotide polymorphisms can be used to adjust a man's measured prostate specific antigen concentration and potentially delay or prevent unnecessary prostate biopsies in Caucasian men.
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