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Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases


Helfand, BT and Roehl, KA and Cooper, PR and McGuire, BB and Fitzgerald, LM and Cancel-Tassin, G and Cornu, J-N and Bauer, S and Van Blarigan, EL and Chen, X and Duggan, D and Ostrander, EA and Gwo-Shu, M and Zhang, Z-F and Chang, S-C and Jeong, S and Fontham, ETH and Smith, G and Mohler, JL and Berndt, SI and McDonnell, SK and Kittles, R and Rybicki, BA and Freedman, M and Kantoff, PW and Pomerantz, M and Breyer, JP and Smith, JR and Rebbeck, TR and Mercola, D and Isaacs, WB and Wiklund, F and Cussenot, O and Thibodeau, SN and Schaid, DJ and Cannon-Albright, L and Cooney, KA and Chanock, SJ and Stanford, JL and Chan, JM and Witte, J and Xu, J and Bensen, JT and Taylor, JA and Catalona, WJ, Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases, Human Genetics, 134, (4) pp. 439-450. ISSN 0340-6717 (2015) [Refereed Article]

Copyright Statement

Springer-Verlag Berlin Heidelberg 2015

DOI: doi:10.1007/s00439-015-1534-9


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.

Item Details

Item Type:Refereed Article
Keywords:Prostate Cancer
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Cancer genetics
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
ID Code:104106
Year Published:2015
Web of Science® Times Cited:33
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-11-03
Last Modified:2017-11-06

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