PURPOSE: Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms (SNPs) associated with prostate cancer risk.
Some of these same genetic variants are also associated with serum PSA levels and lower urinary tract symptoms, raising the question whether the SNPs are truly biomarkers for prostate cancer or simply lead to detection bias. We therefore sought to determine whether the prostate cancer risk SNPs are more strongly associated with tumor volume or prostate volume.
MATERIALS AND METHODS: The genotypes of 38 validated prostate cancer risk SNPs were determined in 1,321 Caucasian men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship between SNP frequency, total prostate volume and tumor volume.
RESULTS: On multivariate analysis, 2 SNPs on chromosome 8q24, rs16901979 (A) (p=0.01) and rs6983267 (G) (p=0.02), were significantly associated with increased tumor volume. In contrast, rs17632542 (T) (p=0.02), near the PSA gene on 19q13, was associated with significantly lower tumor volume, and rs10788160 (A) (p=0.01) on 10q26 was associated with a significantly larger prostate volume.
CONCLUSIONS: Analyses of 38 prostate cancer risk SNPs demonstrates a significant association between several SNPs on chromosome 8q24 and increased tumor volume but not prostate volume, suggesting they are bona fide markers for prostate cancer susceptibility and possibly more aggressive disease. Meanwhile, other "prostate cancer risk SNPs" are associated with PSA levels and either increased prostate volume or decreased tumor volume, suggesting a detection bias due to their phenotypic influence.
Written by:
Reinhardt D, Helfand BT, Cooper PR, Roehl KA, J Catalona W, Loeb S. Are you the author?
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL; Division of Urology, Northshore University Healthcare System, Evanston, IL; Department of Urology and Population Health, New York University and Manhattan VA, New York, NY.
Reference: J Urol. 2013 Dec 14. pii: S0022-5347(13)06128-4.
doi: 10.1016/j.juro.2013.12.030
PubMed Abstract
PMID: 24345439
