Abstract
Incidence rates of pancreatic cancer are increasing worldwide. The lack of screening tools, late-stage diagnosis, and resistance to chemo and radiation therapies make pancreatic cancer the fourth leading cancer-related killer. Recently, awareness has increased about obesity as a strong yet modifiable risk factor for pancreatic cancer. The prevalence of pancreatic ductal adenocarcinoma (PDAC) was significantly higher among obese patients with a body mass index of more than 35 who did not undergo bariatric surgery versus their counterparts. Global obesity rates have increased considerably over the past decades, especially since the coronavirus pandemic. There is still a lack of understanding of the mechanisms of obesity-related PDAC. Emerging evidence suggests that chronic inflammation, circulatory lipids, insulin resistance, adipokines and cytokines release, oxidative stress, and changes in the microbiome associated with obesity are linked to its initiation and progression. Obesity also potentiates driver mutations, including Kirsten Rat Sarcoma viral oncogene (Kras) in PDAC. It is also unclear why obese patients have poorer postoperative outcomes than nonobese PDAC patients highlighting the need for better mechanistic understanding. In this chapter, we aim to provide clinicians and researchers with a comprehensive overview of the carcinogenic pathogenesis of obesity in PDAC and its implications for prevention and treatment.