Multiplicative Model Of Prostate Cancer Susceptibility Alleles On 8q24 AND 17q: Which Combination Is Associated With Aggressive Cancer?
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ORLANDO, FL (UroToday) – A collection of 5 single-nucleotide polymorphisms (SNPs) at 8q24 (3 total), 17q12, and 17q24 has received much attention. A publication in NEJM in January of 2008 demonstrated that this combination of SNPs together with family history had a significant relationship with development of prostate cancer.
In the current study, Helfand and colleagues set out to examine the interplay between these five chromosomal regions. Presence of the SNPs in question was assessed for 575 Caucasian male patients who underwent radical retropubic prostatectomy and consented to genetic testing. Statistical analysis was undertaken to evaluate the association between genetic characteristics and tumor features.
Greater than 99% of the study population were carriers for at least 1 of the 5 alleles with the two SNPs on 17q being the most prevalent. The investigators were able to show that carriers of a larger number of SNPs were more likely to harbor aggressive disease. For instance, if a patient had at least 3 of the 5 alleles they at a significantly higher risk for Gleason 7 or higher disease, positive surgical margins, and seminal vesicle invasion. The less frequent alleles at 8q24 as compared to SNPs at 17q had a stronger association with high risk CaP.
This study by a talented group of investigators is the first report to document a “complex multiplicative interaction” between the five SNPs at 8q24 and 17q.
Presented by Brian T Helfand, MD, et al., at the Annual Meeting of the American Urological Association (AUA) – May 17 – 22, 2008. Orange County Convention Center – Orlando, Florida, USA.
Reported by UroToday Contributing Editor Alexander Kutikov, MD
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