Analysis of over 140,000 European descendants identifies genetically-predicted blood protein biomarkers associated with prostate cancer risk.

Abstract

Several blood protein biomarkers have been associated with prostate cancer (PrCa) risk. However, most studies assessed only a small number of biomarkers and/or included a small sample size. To identify novel protein biomarkers of PrCa risk, we studied 79,194 cases and 61,112 controls of European ancestry, included in the PRACTICAL/ELLIPSE consortia, using genetic instruments of protein quantitative trait loci (pQTLs) for 1,478 plasma proteins. 31 proteins were associated with PrCa risk including proteins encoded by GSTP1, whose methylation level was shown previously to be associated with PrCa risk, and MSMB, SPINT2, IGF2R, and CTSS, which were previously implicated as potential target genes of PrCa risk variants identified in genome-wide association studies. 18 proteins inversely correlated and 13 positively correlated with PrCa risk. For 28 of the identified proteins, gene somatic changes of short indels, splice site, nonsense, or missense mutations were detected in PrCa patients in The Cancer Genome Atlas. Pathway enrichment analysis showed that relevant genes were significantly enriched in cancer related pathways. In conclusion, this study identifies 31 candidates of protein biomarkers for PrCa risk and provides new insights into the biology and genetics of prostate tumorigenesis.