A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Abstract

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three novel susceptibility loci were revealed at P<5×10-8; 15 variants were identified among men of European ancestry, 7 from multiethnic analyses and one was associated with early-onset prostate cancer. These 23 variants, in combination with the known prostate cancer risk variants, explain 33% of the familial risk of the disease in European ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the utility of combining ancestrally diverse populations to discover risk loci for disease.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

“…Genetic correlation was considered statistically significant if the two-sided test statistic provided a P value below .01. To estimate heritability attributable to undiscovered loci, we identified SNPs (Supplementary Table 1, available online) from the National Human Genome Research Institute (NHGRI) catalog or from recent publications (18)(19)(20) that were associated with a given cancer (P < 5x10 -8 ) and removed all SNPs within 250 KB of those loci prior to calculation of the genetic relation matrix. A description of the GCTA methodology, determining FRR, and sensitivity analyses are provided in the Supplementary Methods (available online).…”

Assessing the role of insulin‐like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels

“…Imputation of ∼17 million SNPs/indels using the 1000 Genomes Project (version 3, March 2012 release) as a reference panel was performed with the program IMPUTE v.2 20. Polymorphisms with quality information scores of ( r 2 ) > 0.3 and MAF > 0.5 were taken forward for analysis 23. Overall there were 22,992 prostate cancer cases and 22,936 controls with genotype data available.…”

Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

“…Single nucleotide polymorphisms (SNPs) in several genetic loci like 8q24, 22q13 and 17q12 were reported to be linked to PCa susceptibility, early onset of the disease and tumor agressiveness (Al Olama, et al, 2014; Berndt, et al, 2015; Chang, et al, 2009; Cheng, et al, 2009; Eeles, et al, 2009; Eeles, et al, 2013; Gudmundsson, et al, 2009; Helfand, et al, 2015; Levin, et al, 2008; Salinas, et al, 2008; Schumacher, et al, 2011; Takata, et al, 2010; Thomas, et al, 2008; Witte, 2007). Although little is known about the functional aspect of risk SNPs, some studies showed cancer SNPs predominately present in multiple putative regulatory elements (2011; Sille, et al, 2012).…”