Abstract

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments. METHODS: To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci. RESULTS: , which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production. CONCLUSIONS: We identified 38 candidates of protein biomarkers for PDAC risk. IMPACT: This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.

Authors	Zhu, Jingjing; Shu, Xiang; Guo, Xingyi; Liu, Duo; Bao, Jiandong; Milne, Roger L; Giles, Graham G; Wu, Chong; Du, Mengmeng; White, Emily; Risch, Harvey A; Malats, Nuria; Duell, Eric J; Goodman, Phyllis J; Li, Donghui; Bracci, Paige; Katzke, Verena; Neale, Rachel E; Gallinger, Steven; Van Den Eeden, Stephen K; Arslan, Alan A; Canzian, Federico; Kooperberg, Charles; Beane Freeman, Laura E; Scelo, Ghislaine; Visvanathan, Kala; Haiman, Christopher A; Le Marchand, Loïc; Yu, Herbert; Petersen, Gloria M; Stolzenberg-Solomon, Rachael; Klein, Alison P; Cai, Qiuyin; Long, Jirong; Shu, Xiao-Ou; Zheng, Wei; Wu, Lang
Journal	Cancer Epidemiology Biomarkers and Prevention
Pages	1501-1508
Volume	29
Date	1/05/2020
Grant ID	HHSN268201600018C
Funding Body	NHLBI NIH HHS
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1158/1055-9965.EPI-20-0091