Novel approaches for classification, including molecular features, are needed to direct therapy for men with low-grade prostate cancer (PCa), especially men on active surveillance. Risk alleles identified from genome-wide association studies (GWAS) could improve prognostication. Those risk alleles that coincided with genes and somatic copy number aberrations associated with progression of PCa were selected as the most relevant for prognostication. In a systematic literature review, a total of 698 studies were collated. Fifty-three unique SNPs residing in 29 genomic regions, including 8q24, 10q11 and 19q13, were associated with PCa progression. Functional studies implicated 21 of these single nucleotide polymorphisms (SNPs) as modulating the expression of genes in the androgen receptor pathway and several other oncogenes. In particular, 8q24, encompassingMYC, harbours a high density of SNPs conferring unfavourable pathological characteristics in low-grade PCa, while a copy number gain ofMYCin low-grade PCa was associated with prostate-specific antigen recurrence after radical prostatectomy. By combining GWAS data with gene expression and structural rearrangements, risk alleles were identified that could provide a new basis for developing a prognostication tool to guide therapy for men with early prostate cancer.
Oncotarget. 2018 Feb 05*** epublish ***
Salpie Nowinski, Aida Santaolalla, Ben O'Leary, Massimo Loda, Ayesha Mirchandani, Mark Emberton, Mieke Van Hemelrijck, Anita Grigoriadis
Cancer Bioinformatics, Innovation Hub, Guy's Cancer Centre, King's College London, London, UK., Translational Oncology & Urology Research, King's College London, London, UK., Breast Cancer NOW Centre, The Institute of Cancer Research, The Royal Marsden Hospital, London, UK., Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Division of Surgery and Interventional Science, University College London, London, UK.