Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Apr;134(4):439-50.
doi: 10.1007/s00439-015-1534-9. Epub 2015 Feb 26.

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  1 , 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
Affiliations

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 et al. Hum Genet. 2015 Apr.

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.

PubMed Disclaimer

References

    1. Ahn J, Kibel AS, Park JY, Rebbeck TR, Rennert H, Stanford JL, Ostrander EA, Chanock S, Wang MH, Mittal RD, Isaacs WB, Platz EA, Hayes RB. Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence. Clin Cancer Res. 2011;17:1075–81. doi: 10.1158/1078-0432.CCR-10-0881. 1078-0432.CCR-10-0881 [pii] - DOI - PMC - PubMed
    1. Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Roder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Wokolorczyk D, Kluzniak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, et al. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet. 2014 doi: 10.1038/ng.3094. - DOI - PMC - PubMed
    1. Amin Al Olama A, Kote-Jarai Z, Schumacher FR, Wiklund F, Berndt SI, Benlloch S, Giles GG, Severi G, Neal DE, Hamdy FC, Donovan JL, Hunter DJ, Henderson BE, Thun MJ, Gaziano M, Giovannucci EL, Siddiq A, Travis RC, Cox DG, Canzian F, Riboli E, Key TJ, Andriole G, Albanes D, Hayes RB, Schleutker J, Auvinen A, Tammela TL, Weischer M, Stanford JL, Ostrander EA, Cybulski C, Lubinski J, Thibodeau SN, Schaid DJ, Sorensen KD, Batra J, Clements JA, Chambers S, Aitken J, Gardiner RA, Maier C, Vogel W, Dork T, Brenner H, Habuchi T, Ingles S, John EM, Dickinson JL, Cannon-Albright L, Teixeira MR, Kaneva R, Zhang HW, Lu YJ, Park JY, Cooney KA, Muir KR, Leongamornlert DA, Saunders E, Tymrakiewicz M, Mahmud N, Guy M, Govindasami K, O’Brien LT, Wilkinson RA, Hall AL, Sawyer EJ, Dadaev T, Morrison J, Dearnaley DP, Horwich A, Huddart RA, Khoo VS, Parker CC, Van As N, Woodhouse CJ, Thompson A, Dudderidge T, Ogden C, Cooper CS, Lophatonanon A, Southey MC, Hopper JL, English D, Virtamo J, Le Marchand L, Campa D, Kaaks R, Lindstrom S, Diver WR, Gapstur S, Yeager M, Cox A, Stern MC, Corral R, Aly M, Isaacs W, Adolfsson J, Xu J, Zheng SL, et al. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease. Hum Mol Genet. 2013;22:408–15. doi: 10.1093/hmg/dds425. - DOI - PMC - PubMed
    1. Amundadottir LT, Sulem P, Gudmundsson J, Helgason A, Baker A, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Cazier JB, Sainz J, Jakobsdottir M, Kostic J, Magnusdottir DN, Ghosh S, Agnarsson K, Birgisdottir B, Le Roux L, Olafsdottir A, Blondal T, Andresdottir M, Gretarsdottir OS, Bergthorsson JT, Gudbjartsson D, Gylfason A, Thorleifsson G, Manolescu A, Kristjansson K, Geirsson G, Isaksson H, Douglas J, Johansson JE, Balter K, Wiklund F, Montie JE, Yu X, Suarez BK, Ober C, Cooney KA, Gronberg H, Catalona WJ, Einarsson GV, Barkardottir RB, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K. A common variant associated with prostate cancer in European and African populations. Nat Genet. 2006;38:652–8. doi: 10.1038/ng1808. - DOI - PubMed
    1. Andriole GL, Crawford ED, Grubb RL, 3rd, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL, Yokochi LA, O’Brien B, Clapp JD, Rathmell JM, Riley TL, Hayes RB, Kramer BS, Izmirlian G, Miller AB, Pinsky PF, Prorok PC, Gohagan JK, Berg CD. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310–9. doi: 10.1056/NEJMoa0810696. NEJMoa0810696 [pii] - DOI - PMC - PubMed