TY - JOUR
T1 - Associations of prostate cancer risk variants with disease aggressiveness
T2 - results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases
AU - Helfand, Brian T.
AU - Roehl, Kimberly A.
AU - Cooper, Phillip R.
AU - McGuire, Barry B.
AU - Fitzgerald, Liesel M.
AU - Cancel-Tassin, Geraldine
AU - Cornu, Jean Nicolas
AU - Bauer, Scott
AU - Van Blarigan, Erin L.
AU - Chen, Xin
AU - Duggan, David
AU - Ostrander, Elaine A.
AU - Gwo-Shu, Mary
AU - Zhang, Zuo Feng
AU - Chang, Shen Chih
AU - Jeong, Somee
AU - Fontham, Elizabeth T.H.
AU - Smith, Gary
AU - Mohler, James L.
AU - Berndt, Sonja I.
AU - McDonnell, Shannon K.
AU - Kittles, Rick
AU - Rybicki, Benjamin A.
AU - Freedman, Matthew
AU - Kantoff, Philip W.
AU - Pomerantz, Mark
AU - Breyer, Joan P.
AU - Smith, Jeffrey R.
AU - Rebbeck, Timothy R.
AU - Mercola, Dan
AU - Isaacs, William B.
AU - Wiklund, Fredrick
AU - Cussenot, Olivier
AU - Thibodeau, Stephen N.
AU - Schaid, Daniel J.
AU - Cannon-Albright, Lisa
AU - Cooney, Kathleen A.
AU - Chanock, Stephen J.
AU - Stanford, Janet L.
AU - Chan, June M.
AU - Witte, John
AU - Xu, Jianfeng
AU - Bensen, Jeannette T.
AU - Taylor, Jack A.
AU - Catalona, William J.
N1 - Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/3/10
Y1 - 2015/3/10
N2 - 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.
AB - 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.
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U2 - 10.1007/s00439-015-1534-9
DO - 10.1007/s00439-015-1534-9
M3 - Article
C2 - 25715684
AN - SCOPUS:84925506732
SN - 0340-6717
VL - 134
SP - 439
EP - 450
JO - Human genetics
JF - Human genetics
IS - 4
ER -