Energy balance and gastrointestinal cancer: risk, interventions, outcomes and mechanisms

Abstract

Obesity increases the risk of multiple gastrointestinal cancers and worsens disease outcomes. Conversely, strong inverse associations have emerged between physical activity and colon cancer and possibly other gastrointestinal malignancies. The effect of weight loss interventions - such as modifications of diet and/or physical activity or bariatric surgery - remains unclear in patients who are obese and have gastrointestinal cancer, although large clinical trials are underway. Human intervention studies have already shed light on potential mechanisms underlying the energy balance-cancer relationship, with preclinical models supporting emerging pathway effects. Central to interventions that reduce obesity or increase physical activity are pluripotent cancer-preventive effects (including reduced systemic and adipose tissue inflammation and angiogenesis, altered adipokine levels and improved insulin resistance) that directly interface with the hallmarks of cancer. Other mechanisms, such as DNA repair, oxidative stress and telomere length, immune function, effects on cancer stem cells and the microbiome, could also contribute to energy balance effects on gastrointestinal cancers. Although some mechanisms are well understood (for instance, systemic effects on inflammation and insulin signalling), other areas remain unclear. The current state of knowledge supports the need to better integrate mechanistic approaches with preclinical and human studies to develop effective, personalized diet and exercise interventions to reduce the burden of obesity on gastrointestinal cancer.

Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics

“…2 For both arms, the follow-up mean is significantly less than the baseline mean. 3 For the weight loss intervention arm only, the follow-up mean is significantly less than the baseline mean; in addition, the follow-up mean for the weight loss intervention arm is significantly less than the follow-up mean for the wait-list control arm. 4 For the weight loss intervention arm only, the follow-up mean is significantly greater than the baseline mean; in addition, the follow-up mean for the weight loss intervention arm is significantly greater than the follow-up mean for the wait-list control arm.…”

“…2 For the weight loss intervention arm only, the follow-up mean is significantly greater than the baseline mean. 3 For the weight loss intervention arm only, the follow-up mean is significantly less than the baseline mean. 4 All tumor-related analyses were repeated adjusting for stage (DCIS/Invasive); results were very similar to values in this table, and are not presented separately.…”

“…Obesity is related to poorer prognosis, with a meta‐analysis of 82 studies among 213,075 breast cancer patients showing significantly reduced overall and disease‐specific survival in both pre and postmenopausal obese women, with increased risks ranging from 8% to 29% . A variety of mechanisms that link obesity to cancer progression have been identified and include inflammation, glucoregulation and sex hormones and their interconnecting signaling pathways . Therefore, weight loss is a potential multitargeted therapeutic strategy to slow disease progression, and has been suggested for women with precursor lesions (DCIS), and those with invasive disease…”

“…2 A variety of mechanisms that link obesity to cancer progression have been identified and include inflammation, glucoregulation and sex hormones and their interconnecting signaling pathways. 3 Therefore, weight loss is a potential multitargeted therapeutic strategy to slow disease progression, and has been suggested for women with precursor lesions (DCIS), and those with invasive disease. 4 Limited research shows that weight loss interventions (WLIs) are safe for breast cancer survivors and improve health-related quality-of-life in the short-term.…”

Endocrine-exocrine signaling drives obesity-associated pancreatic ductal adenocarcinoma

“…3) steroid sex hormones (Murphy et al, 2018;Ulrich et al, 2018). Of these mechanisms, epidemiologic studies support a role for both insulin/IGF1 and adipokines in pancreatic cancer development, as elevated levels of insulin, proinsulin, and leptin and low levels of IGF binding protein-1 and adiponectin are associated with increased PDAC risk (Babic et al, 2016;Bao et al, 2013a;Bao et al, 2013b;Wolpin et al, 2013;Wolpin et al, 2007).…”