Genetic Variants And Family History Predict Prostate Cancer Similar To Prostate-Specific Antigen

In the February 1, 2009 issue of Clinical Cancer Research, Dr. S. Lilly Zheng and colleagues tested the hypothesis that a combination of genetic variants associated with prostate cancer (CaP) risk has predictive performance similar to PSA testing.

The work is based upon identification of genetic variants in the form of single nucleotide polymorphisms (SNPs) that were identified by genome-wide association studies and correlate with a man's risk of developing CaP. Specifically, five SNPs identified from 19 SNPs implicated in other studies and tested in a population of Swedish men were modeled using unconditional logistic regression with adjustment for age and geographic region. The sensitivity, specificity and overall predictive performance of predictive models for CaP were evaluated by construction of receiver operating characteristic curves and calculation of the AUC statistics.

Among the 5 major SNPs tested, 3 were located at 8q24, 1 at 7q12, and 1 at 17q24.3. These variants were combined with a family history of CaP in the models. In the final model, a total of 22 risk alleles from the SNPs and a positive family history provided a sensitivity of 0.25 and specificity of 0.86 that were similar to that of the PSA level cutoff of 4.1ng/ml. About 14% of the controls have 11 or more of these 23 risk factors. However, the researchers could find no differences in the results when sensitivity and specificity of the genetic risk factors were used to predict for the aggressiveness of CaP, early age-diagnosed CaP or late-age diagnosed CaP. A model using age, family history, and the 11 risk SNPs had an AUC of 0.65, better than the 0.50 level that represents chance alone and similar to the 0.68 for PSA.

Zheng SL, Sun J, Wiklund F, Gao Z, Stattin P, Purcell LD, Adami HO, Hsu FC, Zhu Y, Adolfsson J, Johansson JE, Turner AR, Adams TS, Liu W, Duggan D, Carpten JD, Chang BL, Isaacs WB, Xu J, Grönberg H
Clin Cancer Res. 2009 Feb 1;15(3):1105-11
10.1158/1078-0432.CCR-08-1743

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS