Literature DB >> 32439797

Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk.

Jingjing Zhu1, Xiang Shu2, Xingyi Guo2, Duo Liu1,3, Jiandong Bao2, Roger L Milne4,5,6, Graham G Giles4,5,6, Chong Wu7, Mengmeng Du8, Emily White9,10, Harvey A Risch11, Nuria Malats12, Eric J Duell13, Phyllis J Goodman14, Donghui Li15, Paige Bracci16, Verena Katzke17, Rachel E Neale18, Steven Gallinger19, Stephen K Van Den Eeden20, Alan A Arslan21, Federico Canzian22, Charles Kooperberg9, Laura E Beane Freeman23, Ghislaine Scelo24, Kala Visvanathan25, Christopher A Haiman26, Loïc Le Marchand1, Herbert Yu1, Gloria M Petersen27, Rachael Stolzenberg-Solomon23, Alison P Klein25,28, Qiuyin Cai2, Jirong Long2, Xiao-Ou Shu2, Wei Zheng2, Lang Wu29.   

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: We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by ABO, 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. ©2020 American Association for Cancer Research.

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Year:  2020        PMID: 32439797      PMCID: PMC7334065          DOI: 10.1158/1055-9965.EPI-20-0091

Source DB:  PubMed          Journal:  Cancer Epidemiol Biomarkers Prev        ISSN: 1055-9965            Impact factor:   4.090


  47 in total

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