The Digestive Diseases and Microbiota group of the Institute for Biomedical Research of Girona Dr. Josep Trueta (IDIBGI) has investigated the role of certain biomarkers of oxidative stress and inflammation in the development of pancreatic cancer and chronic pancreatitis. The results of this study, published in the Journal of Clinical Medicine, allow these biomarkers to be ruled out as targets for treatment to prevent pancreatic disease. However, the conclusions leave the door open to examine whether these biomarkers could serve as potential non-invasive tools for early diagnosis.
Currently, the main problem with pancreatic malignancy is its lack of specific symptoms, which are also associated with many other diseases and present in advanced stages. This complicates prevention and clinical diagnosis, and also worsens the prognosis, i.e. the evolution of the disease. The identification of causal risk factors for pancreatic malignancy is important because it allows the development of intervention strategies to prevent them.
In this article in the Journal of Clinical Medicine, the IDIBGI's Digestive Diseases and Microbiota group, led by Dr. Xavier Aldeguer, analyses the associations between biomarkers of inflammation, oxidative stress and intestinal permeability with pancreatic diseases. These biomarkers are related to dysregulation processes that occur when there is a chronic disease, such as chronic pancreatitis, or the presence of a tumour, as in the case of pancreatic cancer. It is also believed that this dysregulation and inflammation is associated with the malignancy and promotes tumour development and progression. For this reason, this research also assesses whether the observed associations have a causal effect on pancreatic malignancy, in order to determine its use as a preventive tool.
The serological results of the study indicate that patients with chronic pancreatitis and pancreatic cancer are less able to regulate oxidative stress compared to controls. However, a lower level of activity of oxidative stress regulating enzymes is associated with a higher risk of chronic pancreatitis, but not of pancreatic cancer. Similarly, higher levels of cellular damage are associated with increased risk of chronic pancreatitis only.
When the causal relationship of these observed associations with chronic pancreatitis is explored, it is observed that it is not a causal relationship; which informs us that these biomarkers are not a good option as aids for its prevention. Nevertheless, the study opens the door to a possible relationship between these biomarkers and chronic pancreatitis, which implies continuing to investigate their potential as early diagnostic tools in clinical practice.
Methodologically, this study uses Mendelian randomisation as an alternative to randomised controlled trials when studying the causality of the associations identified between biomarkers and chronic pancreatitis. This is because randomised controlled trials are very costly and complex to implement. One of the main problems of these trials is that all external factors (environmental and demographic) that may influence the development of a disease and that are not equally distributed among the study population must be controlled as far as possible.
In contrast, Mendelian randomisation uses genetic variants that are strongly associated with the biomarkers to be studied, in this study they are the activity of two enzymes that regulate oxidative stress and the levels of a marker that determines cell damage. The genetic variants found that are associated with these biomarkers are randomly distributed in the population, generating groups of people with more or less genetic predisposition to enzyme activity and levels of cell damage.
Thus, by studying the distribution of these genetic variants in a population where there are groups of patients with pancreatic malignancy and controls without it is possible to know whether the biomarker is causally associated with the malignancy. The external factors that may influence the study of causal association between the biomarker and the disease are equally distributed in the case of Mendelian randomisation, since the genetic variants associated with the biomarker are independent of each other.
This work stems from a project funded by the Marató de TV3 603/C/2019, of which the Institut d'Investigació Biomèdica de Girona (IDIBGI) and the Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) are part.
Reference article: Vilà-Quintana L, Fort E, Pardo L, Albiol-Quer MT, Ortiz MR, Capdevila M, Feliu A, Bahí A, Llirós M, Aguilar E, et al. Exploring the Associations of Inflammatory and Oxidative Stress Biomarkers with Pancreatic Diseases: An Observational and Mendelian Randomisation Study. Journal of Clinical Medicine. 2024; 13(8):2247.
DOI: https://doi.org/10.3390/jcm13082247
