Pancreatic Cancer and the Obesity Epidemic: A Narrative Review

Abstract

Pancreatic cancer (PC) is one of the most frequent causes of death. It usually affects older individuals with incidence closely approaching mortality due to its early asymptomatic feature and highly metastatic nature. Multiple risk factors such as family history, smoking, and germline mutations are associated with PC development, with obesity being one of the controllable factors. This review article focuses on the compilation of various studies to help establish a correlation between obesity or an increased body mass index and PC development. Hence, in this review, we have summarised multiple biological mechanisms of PC development induced by obesity, including insulin resistance, inflammation, beta-cell dysfunction, and oxidative stress, to prove that their correlation when combined with other factors, such as smoking, alcohol and chronic pancreatitis, may increase its risk. We have also reviewed potential diagnostic and screening techniques, such as evaluating precancerous lesions in high-risk patients and management plans discussing upcoming advances in treatment tactics such as neoadjuvant therapy, to reduce post-operative complications.

Keywords: chronic pancreatitis; diabetes mellitus type 2; malignant pancreatic cancer; obesity-related illnesses; type b insulin resistance.

Figure 1. Inflammatory mediators and the pathways leading to insulin resistance

ROS, reactive oxygen species; TNFR, tumor necrosis factor-receptor; IL6-R, interleukin 6-receptor; ER, endoplasmic reticulum; JNK, c-Jun N-terminal kinase; IKKβ/NF-κB, inhibitory-κB kinase/nuclear factor-κB

Figure 2. Pathogenesis of hyperinsulinemia-induced cell proliferation

IGF-1, insulin-like growth factor-1; IGF-1 R, IGF-1 receptor; IRS, insulin receptor substrate; PI3K, phosphatidylinositol 3-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol 3,4,5-triphosphate; PDK-1, 3-phosphoinositide-dependent protein kinase 1; AKT/PKB, protein kinase B; mTORC1, mammalian target of rapamycin complex 1; S6K, p70 ribosomal S6 kinase