Immune Markers and Risk of Pancreatic Cancer in the European
EPIC
Cohort
Verena A. Katzke, Yue Chen, Srimanti Dutta, Federico Canzian, Julie Louise Munk Andersen, Agnetha Linn Rostgaard‐Hansen, Léa Bouteille, Vinciane Rebours, Thérèse Truong, Matthias B. Schulze, Benedetta Bendinelli, Valeria Pala, Vittorio Simeon, Rosario Tumino, Carlotta Sacerdote, Roel Vermeulen, P. Martijn Kolijn, Sjoerd G. Elias, Marta Crous‐Bou, Maria‐José Sánchez, Ana Jimenez‐Zabala, José María Huerta, Marcela Guevara, Nick Wareham, Marie Breeur, Mattias Johansson, James Yarmolinsky, Daniele Campa, Rudolf Kaaks ABSTRACT
The immune system is a major driver in pancreatic cancer development. Several prospective cohort studies have found associations for single immune system‐derived proteins such as IL6 or CRP, but results are inconclusive, and Omics‐based research is scarce. Hence, we aimed to investigate associations of a comprehensive protein panel with the risk of pancreatic cancer. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 92 immune proteins were measured in baseline blood samples of 406 incident pancreatic cancer cases and 406 sex‐ and age‐matched controls, using the Olink Immuno‐Oncology panel. Multivariable adjusted conditional logistic regression was used to estimate odds ratios (OR, 95% CI) for protein levels in association with pancreatic cancer risk. Eight biomarkers were associated with pancreatic cancer risk (MMP12, LAMP3, CD28, IL‐6, IL‐12, FASLG, PD‐L2, and PDCD1) but only MMP12 was significantly associated after multivariable adjustments for confounders and the seven proteins, with OR = 1.56 (95% CI: 1.20–2.03) for a doubling in protein concentration. After correction for multiple testing, none of the proteins were associated with risk. Restricting analyses to cases diagnosed within the first 4 years and 4–8 years after recruitment resulted in OR of 1.89 (95% CI: 1.28–2.80) and 1.37 (95% CI: 1.01–1.86) for MMP12, respectively. Higher levels of MMP12 were associated with pancreatic cancer risk specifically in those diagnosed shortly after recruitment, while other immune‐related factors were not associated with risk. Further cohort studies are needed to confirm our initial findings.