Abstract

Pancreatic cancer (PaCa) is still one of the deadliest cancers in the world, and there is an increased incidence of it following the global obesity epidemic. This systematic review included the latest research on the association of obesity with PaCa, as well as recent studies that use cutting-edge methodological techniques to address confounding and to shed light on causal mechanisms. Under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, 17 studies met the inclusion criteria. Mendelian randomization criteria and the Newcastle-Ottawa Scale were used to measure quality. The obesity-cancer association became apparent in young adults (20-39 years old) and was nearly twofold higher in those who were class II obese (adjusted HR 1.958). Metabolomic analyses revealed that valine is a mediator that accounted for approximately 19% of the obesity-cancer association. Abdominal adiposity might be a more important causal factor than total body mass index. The metabolic dysfunctions induced by obesity were more likely to be linked to the risk of PaCa than the metabolic dysfunctions induced by a high body mass index (BMI) alone. Abdominal adiposity and metabolic health status were found to be more important factors than BMI alone. The importance of early weight management therapies was found to be underscored by the preventive effect that bariatric surgery has and the dose-response relationship between the severity of obesity and the age at diagnosis of PaCa. Metabolic health assessment should be incorporated with the traditional anthropometric assessment in risk stratification to identify high-risk group(s) for targeted preventive interventions.

Key words: Pancreatic cancer, obesity, body mass index, adiposity, early-onset pancreatic cancer, systematic review