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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.

Publication ,  Journal Article
Helfand, BT; Roehl, KA; Cooper, PR; McGuire, BB; Fitzgerald, LM; Cancel-Tassin, G; Cornu, J-N; Bauer, S; Van Blarigan, EL; Chen, X; Duggan, D ...
Published in: Hum Genet
April 2015

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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Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

April 2015

Volume

134

Issue

4

Start / End Page

439 / 450

Location

Germany

Related Subject Headings

  • United States
  • Risk Factors
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Neoplasm Invasiveness
  • National Cancer Institute (U.S.)
  • Middle Aged
  • Male
  • Humans
  • Genetics & Heredity
 

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Helfand, B. T., Roehl, K. A., Cooper, P. R., McGuire, B. B., Fitzgerald, L. M., Cancel-Tassin, G., … 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. Hum Genet, 134(4), 439–450. https://doi.org/10.1007/s00439-015-1534-9
Helfand, Brian T., Kimberly A. Roehl, Phillip R. Cooper, Barry B. McGuire, Liesel M. Fitzgerald, Geraldine Cancel-Tassin, Jean-Nicolas Cornu, et al. “Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases.Hum Genet 134, no. 4 (April 2015): 439–50. https://doi.org/10.1007/s00439-015-1534-9.
Helfand BT, Roehl KA, Cooper PR, McGuire BB, Fitzgerald LM, Cancel-Tassin G, et al. Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases. Hum Genet. 2015 Apr;134(4):439–50.
Helfand, Brian T., et al. “Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases.Hum Genet, vol. 134, no. 4, Apr. 2015, pp. 439–50. Pubmed, doi:10.1007/s00439-015-1534-9.
Helfand BT, Roehl KA, Cooper PR, McGuire BB, Fitzgerald LM, Cancel-Tassin G, Cornu J-N, Bauer S, Van Blarigan EL, Chen X, Duggan D, Ostrander EA, Gwo-Shu M, Zhang Z-F, Chang S-C, 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. Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases. Hum Genet. 2015 Apr;134(4):439–450.
Journal cover image

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

April 2015

Volume

134

Issue

4

Start / End Page

439 / 450

Location

Germany

Related Subject Headings

  • United States
  • Risk Factors
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Neoplasm Invasiveness
  • National Cancer Institute (U.S.)
  • Middle Aged
  • Male
  • Humans
  • Genetics & Heredity