RT Journal Article
T1 Are Circulating Immune Cells a Determinant of Pancreatic Cancer Risk? A Prospective Study Using Epigenetic Cell Count Measures.
A1 Katzke, Verena A
A1 Le Cornet, Charlotte
A1 Mahfouz, Rayaan
A1 Brauer, Bianca
A1 Johnson, Theron
A1 Canzian, Federico
A1 Rebours, Vinciane
A1 Boutron-Ruault, Marie-Christine
A1 Severi, Gianluca
A1 Schulze, Matthias B
A1 Olsen, Anja
A1 Tjønneland, Anne
A1 Overvad, Kim
A1 Crous-Bou, Marta
A1 Molina-Montes, Esther
A1 Amiano, Pilar
A1 Huerta, José María
A1 Ardanaz, Eva
A1 Perez-Cornago, Aurora
A1 Masala, Giovanna
A1 Pala, Valeria
A1 Tumino, Rosario
A1 Sacerdote, Carlotta
A1 Panico, Salvatore
A1 Bueno-de-Mesquita, Bas
A1 Vermeulen, Roel
A1 Sund, Malin
A1 Franklin, Oskar
A1 Christakoudi, Sofia
A1 Dossus, Laure
A1 Weiderpass, Elisabete
A1 Olek, Sven
A1 Kaaks, Rudolf
AB Evidence is accumulating that immune cells play a prominent role in pancreatic cancer etiology but prospective investigations are missing. We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sublineages: total CD3+, CD8+, CD4+, and FOXP3+ regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. ORs with 95% confidence intervals were estimated using logistic regressions, modeling relative counts of immune cells on a continuous scale. Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in subgroup analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8+ were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up. These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8+ cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease. We have shown, for the first time, that increased relative counts of regulatory T cells and lower relative counts of CD8+, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development.See related commentary by Michaud and Kelsey, p. 2176.
YR 2021
FD 2021-09-20
LK https://hdl.handle.net/10668/28013
UL https://hdl.handle.net/10668/28013
LA en
DS RISalud
RD Apr 19, 2025