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

Brian T. Helfand; Kimberly A. Roehl; Phillip R. Cooper; Barry B. McGuire; Liesel M. Fitzgerald; Geraldine Cancel-Tassin; Jean Nicolas Cornu; Scott Bauer; Erin L. Van Blarigan; Xin Chen; David Duggan; Elaine A. Ostrander; Mary Gwo-Shu; Zuo Feng Zhang; Shen Chih Chang; Somee Jeong; Elizabeth T.H. Fontham; Gary Smith; James L. Mohler; Sonja I. Berndt; Shannon K. McDonnell; Rick Kittles; Benjamin A. Rybicki; Matthew Freedman; Philip W. Kantoff; Mark Pomerantz; Joan P. Breyer; Jeffrey R. Smith; Timothy R. Rebbeck; Dan Mercola; William B. Isaacs; Fredrick Wiklund; Olivier Cussenot; Stephen N. Thibodeau; Daniel J. Schaid; Lisa Cannon-Albright; Kathleen A. Cooney; Stephen J. Chanock; Janet L. Stanford; June M. Chan; John Witte; Jianfeng Xu; Jeannette T. Bensen; Jack A. Taylor; William J. Catalona

doi:10.1007/s00439-015-1534-9

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

Brian T. Helfand
, Kimberly A. Roehl
, Phillip R. Cooper
, Barry B. McGuire
, Liesel M. Fitzgerald
, Geraldine Cancel-Tassin
, Jean Nicolas Cornu
, Scott Bauer
, Erin L. Van Blarigan
, Xin Chen
, David Duggan
, Elaine A. Ostrander
, Mary Gwo-Shu
, Zuo Feng Zhang
, Shen Chih Chang
, Somee Jeong
, Elizabeth T.H. Fontham
, Gary Smith
, James L. Mohler
, Sonja I. Berndt

Shannon K. McDonnell, Rick Kittles, Benjamin A. Rybicki, Matthew Freedman, Philip W. Kantoff, Mark Pomerantz, Joan P. Breyer, Jeffrey R. Smith, Timothy R. Rebbeck, Dan Mercola, William B. Isaacs, Fredrick Wiklund, Olivier Cussenot, Stephen N. Thibodeau, Daniel J. Schaid, Lisa Cannon-Albright, Kathleen A. Cooney, Stephen J. Chanock, Janet L. Stanford, June M. Chan, John Witte, Jianfeng Xu, Jeannette T. Bensen, Jack A. Taylor, William J. Catalona

Department of Urology

NorthShore University HealthSystem
Northwestern University
Cancer Council Victoria
Assistance publique – Hôpitaux de Paris
University of California at San Francisco
University of California at Irvine
Translational Genomics Research Institute
National Institutes of Health
Dana-Farber Cancer Institute
University of California at Los Angeles
Louisiana State University Health Sciences Center
Roswell Park Cancer Institute
Mayo Clinic Rochester, MN
University of Arizona
Henry Ford Health System
Vanderbilt University
University of Pennsylvania
Johns Hopkins University
Umeå University
University of Utah
University of Michigan, Ann Arbor
Fred Hutchinson Cancer Research Center
University of North Carolina at Chapel Hill

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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.

Original language	English
Pages (from-to)	439-450
Number of pages	12
Journal	Human Genetics
Volume	134
Issue number	4
DOIs	https://doi.org/10.1007/s00439-015-1534-9
State	Published - Mar 10 2015

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Helfand, B. T., Roehl, K. A., Cooper, P. R., McGuire, B. B., Fitzgerald, L. M., Cancel-Tassin, G., Cornu, J. N., Bauer, S., Van Blarigan, E. L., Chen, X., Duggan, D., Ostrander, E. A., Gwo-Shu, M., Zhang, Z. F., Chang, S. C., Jeong, S., Fontham, E. T. H., Smith, G., Mohler, J. L., ... Catalona, W. J. (2015). 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), 439-450. https://doi.org/10.1007/s00439-015-1534-9

@article{f7140f68e18946f488b0afdbcb99eae9,

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

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.",

author = "Helfand, \{Brian T.\} and Roehl, \{Kimberly A.\} and Cooper, \{Phillip R.\} and McGuire, \{Barry B.\} and Fitzgerald, \{Liesel M.\} and Geraldine Cancel-Tassin and Cornu, \{Jean Nicolas\} and Scott Bauer and \{Van Blarigan\}, \{Erin L.\} and Xin Chen and David Duggan and Ostrander, \{Elaine A.\} and Mary Gwo-Shu and Zhang, \{Zuo Feng\} and Chang, \{Shen Chih\} and Somee Jeong and Fontham, \{Elizabeth T.H.\} and Gary Smith and Mohler, \{James L.\} and Berndt, \{Sonja I.\} and McDonnell, \{Shannon K.\} and Rick Kittles and Rybicki, \{Benjamin A.\} and Matthew Freedman and Kantoff, \{Philip W.\} and Mark Pomerantz and Breyer, \{Joan P.\} and Smith, \{Jeffrey R.\} and Rebbeck, \{Timothy R.\} and Dan Mercola and Isaacs, \{William B.\} and Fredrick Wiklund and Olivier Cussenot and Thibodeau, \{Stephen N.\} and Schaid, \{Daniel J.\} and Lisa Cannon-Albright and Cooney, \{Kathleen A.\} and Chanock, \{Stephen J.\} and Stanford, \{Janet L.\} and Chan, \{June M.\} and John Witte and Jianfeng Xu and Bensen, \{Jeannette T.\} and Taylor, \{Jack A.\} and Catalona, \{William J.\}",

note = "Publisher Copyright: {\textcopyright} 2015, Springer-Verlag Berlin Heidelberg.",

year = "2015",

month = mar,

day = "10",

doi = "10.1007/s00439-015-1534-9",

language = "English",

volume = "134",

pages = "439--450",

journal = "Human Genetics",

issn = "0340-6717",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "4",

}

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, ETH, 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 2015, 'Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases', Human Genetics, vol. 134, no. 4, pp. 439-450. https://doi.org/10.1007/s00439-015-1534-9

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.

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.

UR - https://www.scopus.com/pages/publications/84925506732

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 -

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

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