Analysis of Over 140,000 European Descendants Identifies Genetically Predicted Blood Protein Biomarkers Associated with Prostate Cancer Risk.
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Embargo End Date
ICR Authors
Authors
Wu, L
Shu, X
Bao, J
Guo, X
Kote-Jarai, Z
Haiman, CA
Eeles, RA
Zheng, W
PRACTICAL, CRUK, BPC3, CAPS, PEGASUS Consortia,
Shu, X
Bao, J
Guo, X
Kote-Jarai, Z
Haiman, CA
Eeles, RA
Zheng, W
PRACTICAL, CRUK, BPC3, CAPS, PEGASUS Consortia,
Document Type
Journal Article
Date
2019-09-15
Date Accepted
2019-07-17
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.
Citation
Cancer research, 2019, 79 (18), pp. 4592 - 4598
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
0008-5472
eISSN
1538-7445
Research Team
Oncogenetics