Association of prostate cancer risk loci with disease aggressiveness and prostate cancer-specific mortality - Abstract

Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., 44 Binney Street, Boston, MA, 02115, United States.

Genome-wide association studies have detected over 30 inherited prostate cancer (CaP) risk variants. While clearly associated with risk, their relationship with clinical outcome, particularly prostate cancer-specific mortality, is less well known. We investigated whether the risk variants are associated with various measures of disease aggressiveness and prostate cancer-specific mortality. In a cohort of 3,945 men of European ancestry with CaP, we genotyped 36 single nucleotide polymorphisms (SNPs): 35 known CaP risk variants and one SNP (rs4054823) that was recently reported to be associated with CaP aggressiveness. The majority of subjects were diagnosed between 1995 and 2004, and the cohort included a total of 580 CaP-specific deaths. We evaluated associations between the 36 polymorphisms and CaP survival as well as other clinical parameters, including age at diagnosis, prostate-specific antigen (PSA) at diagnosis and Gleason score. Two SNPs, rs2735839 at chromosome 19q13 and rs7679673 at 4q24, were associated with CaP-specific survival (p=7x10-4 and 0.014, respectively). A total of 12 SNPs were associated with other variables (p< 0.05): age at diagnosis, PSA at diagnosis, Gleason score, and/or disease aggressiveness based on D'Amico criteria. Genotype status at rs4054823 was not associated with aggressiveness or outcome. Our results identify two common polymorphisms associated with CaP-specific mortality.

Written by:
Pomerantz M, Werner L, Xie W, Regan MM, Lee GS, Sun T, Evan C, Petrozziello G, Nakabayashi M, Oh WK, Kantoff PW, Freedman ML.   Are you the author?

Reference: Cancer Prev Res (Phila). 2011 Mar 2. Epub ahead of print.
doi: 10.1158/1940-6207.CAPR-10-0292

PubMed Abstract
PMID: 21367958 Prostate Cancer Section