Genetic factors influencing prostate cancer risk in Norwegian men

Norway has one of the highest rates of death due to prostate cancer (PCa) in the world. To assess the contribution of both common and rare single nucleotide variants (SNPs) to the prostate cancer burden in Norway, we assessed the frequency of the established prostate cancer susceptibility allele, HOXB13 G84E, as well as a series of validated, common PCa risk SNPs in a Norwegian PCa population of 779 patients. The G84E allele was observed in 2.3% of patients compared to 0.7% of control individuals, OR = 3.8, P = 1 × 10-4. While there was a trend toward an earlier age at diagnosis, overall the clinicopathologic features of PCa were not significantly different in G84E carriers and non-carriers. Evaluation of 32 established common risk alleles revealed significant associations of risk alleles at 13 loci, including SNPs at 8q24, and near TET2, SLC22A3, NKX3-1, CASC8, MYC, DAP2IP, MSMB, HNF1B, PPP1R14A, and KLK2/3. When the data for each SNP are combined into a genetic risk score (GRS), Norwegian men within the top decile of GRS have over 5-fold greater risk to be diagnosed with PCa than men with GRS in the lowest decile. These results indicate that risk alleles of HOXB13 and common variant SNPs are important components of inherited PCa risk in the Norwegian population, although these factors appear to contribute little to the malignancy's aggressiveness.

The Prostate. 2017 Nov 27 [Epub ahead of print]

Haitao Chen, Charles M Ewing, Sigun Zheng, Eli M Grindedaal, Kathleen A Cooney, Kathleen Wiley, Srdjan Djurovic, Ole A Andreassen, Karol Axcrona, Ian G Mills, Jianfeng Xu, Lovise Maehle, Sophie D Fosså, William B Isaacs

Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois., Brady Urological Institute, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland., Department of Medical Genetics, Oslo University Hospital, Oslo, Norway., Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah., NORMENT, KG Jebsen Centre for Psychosis Research and Department of Medical Genetics, Oslo University Hospital, Oslo, Norway., NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway., Department of Urology, Akershus University Hospital, Lørenskog, Norway., Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, Forskningsparken, University of Oslo, Oslo, Norway., Department of Oncology, Faculty of Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.