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Cancer Res. 2019 Sep 15;79(18):4592-4598. doi: 10.1158/0008-5472.CAN-18-3997. Epub 2019 Jul 23.

Analysis of Over 140,000 European Descendants Identifies Genetically Predicted Blood Protein Biomarkers Associated with Prostate Cancer Risk.

Author information

1
Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
2
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
3
Division of Genetics and Epidemiology, The Institute of Cancer Research, and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
4
Department of Preventive Medicine, University of Southern California, Los Angeles, California.
5
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. wei.zheng@vanderbilt.edu.

Abstract

Several blood protein biomarkers have been associated with prostate cancer risk. However, most studies assessed only a small number of biomarkers and/or included a small sample size. To identify novel protein biomarkers of prostate cancer 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 for 1,478 plasma proteins. A total of 31 proteins were associated with prostate cancer risk including proteins encoded by GSTP1, whose methylation level was shown previously to be associated with prostate cancer risk, and MSMB, SPINT2, IGF2R, and CTSS, which were previously implicated as potential target genes of prostate cancer risk variants identified in genome-wide association studies. A total of 18 proteins inversely correlated and 13 positively correlated with prostate cancer risk. For 28 of the identified proteins, gene somatic changes of short indels, splice site, nonsense, or missense mutations were detected in patients with prostate cancer 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 prostate cancer risk and provides new insights into the biology and genetics of prostate tumorigenesis. SIGNIFICANCE: Integration of genomics and proteomics data identifies biomarkers associated with prostate cancer risk.

PMID:
31337649
PMCID:
PMC6744971
[Available on 2020-03-15]
DOI:
10.1158/0008-5472.CAN-18-3997

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