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Title: Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases.
Authors: Helfand BT,  Roehl KA,  Cooper PR,  McGuire BB,  Fitzgerald LM,  Cancel-Tassin G,  Cornu JN,  Bauer S,  Van Blarigan EL,  Chen X,  Duggan D,  Ostrander EA,  Gwo-Shu M,  Zhang ZF,  Chang SC,  Jeong S,  Fontham ET,  Smith G,  Mohler JL,  Berndt SI,  McDonnell SK,  Kittles R,  Rybicki BA,  Freedman M,  Kantoff PW,  Pomerantz M,  Breyer JP,  Smith JR,  Rebbeck TR,  Mercola D,  Isaacs WB,  Wiklund F,  Cussenot O,  Thibodeau SN,  Schaid DJ,  Cannon-Albright L,  Cooney KA,  Chanock SJ,  Stanford JL,  Chan JM,  Witte J,  Xu J,  Bensen JT,  Taylor JA,  Catalona WJ
Journal: Hum Genet
Date: 2015 Apr
Branches: LGS, LTG, OD, OEEB
PubMed ID: 25715684
PMC ID: not available
Abstract: Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤6, 7, ≥8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness.