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Genetic factors influencing prostate cancer risk in Norwegian men
Author(s) -
Chen Haitao,
Ewing Charles M.,
Zheng Sigun,
Grindedaal Eli M.,
Cooney Kathleen A.,
Wiley Kathleen,
Djurovic Srdjan,
Andreassen Ole A.,
Axcrona Karol,
Mills Ian G.,
Xu Jianfeng,
Maehle Lovise,
Fosså Sophie D.,
Isaacs William B.
Publication year - 2018
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23453
Subject(s) - prostate cancer , single nucleotide polymorphism , medicine , allele , population , cancer , genetics , case control study , oncology , gynecology , genotype , biology , gene , environmental health
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.