Abstract
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, encompassing MYC, harbours a high density of SNPs conferring unfavourable pathological characteristics in low-grade PCa, while a copy number gain of MYC in 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.
Highlights
Prostate cancer (PCa) is the most common cancer in men [1], with around 160,000 new cases each year in the USA alone [2]
A total of 22 PCa genome-wide association studies (GWAS), and GWAS validation studies across different populations were used to identify Single nucleotide polymorphism (SNP) potentially associated with aggressiveness, progression, biochemical recurrence, and metastasis
Nine of these SNPs were significantly associated with aggressive disease or unfavorable characteristics in several population studies, e.g. rs10993994 [16, 44, 36, 40, 41] was significantly associated with aggressiveness in Asian Indian, Ashkenazi, Taiwanese, European, African American, Australian, Canadian and US populations (Supplementary Table 1)
Summary
Prostate cancer (PCa) is the most common cancer in men [1], with around 160,000 new cases each year in the USA alone [2]. Severity is conventionally assessed using Gleason score, prostate specific antigen (PSA) levels and tumour volume [3]. 80% of men in the US with PCa are diagnosed with stage I localised disease many of whom have a low to intermediate risk of progression [4]. Men who present with low-risk PCa as defined by a Gleason score of 6 (3+3) and whose life expectancy is thought to be at least 10 years, are usually managed through active surveillance (AS) [5, 6]. AS aims to reduce over-treatment through monitoring the disease, with the requirement for radical intervention assessed with regular PSA-tests and biopsies rather than intervening at diagnosis [7]. The patient on AS can be redirected to curative treatment in the event of short www.impactjournals.com/oncotarget
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