Association of Obesity-Related Metabolic Disruptions With Cancer Risk and Outcome

Abstract

Over the past 40 years, the prevalence of obesity has increased epidemically worldwide, which raises significant concerns regarding public health and the associated economic burden. Obesity is a major risk factor for several conditions including cardiovascular disease and type 2 diabetes, and recent evidence suggests that obesity negatively affects cancer risk and outcome. The relationship between obesity and cancer is complex and involves multiple factors both at the systemic and cellular level. Indeed, disruptions in insulin metabolism, adipokines, inflammation, and sex hormones all contribute to the adverse effects of obesity in cancer development and progression. The focus of this review will be the impact of these systemic obesity-related factors on cancer biology, incidence, and outcome. Potential therapeutic interventions and current clinical trials targeting obesity and its associated factors will also be discussed.

Effects of a parallel-arm randomized controlled weight loss pilot study on biological and psychosocial parameters of overweight and obese breast cancer survivors

“…C-reactive protein (CRP) is a marker of systemic inflammation and studies have linked increased pre-treatment CRP levels with decreased survival [14, 15] though this finding has not been consistently shown in other studies [16]. Leptin and adiponectin are adipokines that may influence recurrence risk [17]. Women with breast cancer may have dysregulation in several circadian systems, including hormonal rhythms [18] such as secretion of cortisol and melatonin.…”

Cardiometabolic risk factors and survival after breast cancer in the Women's Health Initiative

“…Clustering of cardiovascular risk factors recognized as MetS centers on the premise of insulin resistance that could influence breast cancer pathogenesis and progression through several proposed mechanisms. 28 Adipose tissue has an active role in endocrine signaling through leptin and other adipokines, which may initiate carcinogenesis and progression through their function as growth factors. 36 This process may be in part through activation of downstream signaling of the extracellular signal regulated kinase and signal reducer and activator of transcription 3 pathways by the long form of the leptin receptor.…”

“…[22][23][24][25] The increasing prevalence of MetS and evidence suggesting a relationship between cardiometabolic risk factors and breast cancer risk, potentially through a common shared pathway of altered insulin sensitivity and sex hormonal changes, highlights the importance of understanding the impact of these risk factors on outcomes after breast cancer. 28 The Women's Health Initiative (WHI) cohort provides an opportunity to explore the relationship between exposure to cardiometabolic risk factors and mortality after breast cancer.…”

Favorable 90-Day Mortality in Obese Caucasian Patients with Septic Shock According to the Sepsis-3 Definition

“…In particular, the effect of obesity, one of the most common comorbidities in critically ill patients, on sepsis and septic shock has been examined in various studies [16,17]. Defined by the World Health Organization (WHO) as a BMI ≥ 30 kg/m 2 , obesity is associated with a number of other concomitant comorbidities, such as hypertension, cardiovascular diseases, diabetes mellitus type 2, non-alcoholic fatty liver disease, sleep apnea, and cancer [18,19].…”