Metabolic Surgery and Cancer Risk: An Opportunity for Mechanistic Research

Abstract

Metabolic (bariatric) surgery (MBS) is recommended for individuals with a BMI > 40 kg/m2 or those with a BMI 35–40 kg/m2 who have one or more obesity related comorbidities. MBS leads to greater initial and sustained weight loss than nonsurgical weight loss approaches. MBS provides dramatic improvement in metabolic function, associated with a reduction in type 2 diabetes mellitus and cardiovascular risk. While the number of MBS procedures performed in the U.S. and worldwide continues to increase, they are still only performed on one percent of the affected population. MBS also appears to reduce the risk of certain obesity related cancers, although which cancers are favorably impacted vary by study, who benefits most is uncertain, and the mechanism(s) driving this risk reduction are mostly speculative. The goal of this manuscript is to highlight 1) emerging evidence that MBS influences cancer risk, and that the potential benefit appears to vary based on cancer, gender, surgical procedure, and likely other variables; 2) the role of the NIH in MBS research in T2DM and CV risk for many years, and more recently in cancer; and 3) the opportunity for research to understand the mechanism(s) by which MBS influences cancer. There is evidence that women benefit more from MBS than men, that MBS may actually increase the risk of colorectal cancer in both women and men, and there is speculation that the benefit in cancer risk reduction may vary according to which MBS procedure an individual undergoes. Herein, we review what is currently known, the historical role of government, especially the National Institutes of Health (NIH), in driving this research, and provide suggestions that we believe could lead to a better understanding of whether and how MBS impacts cancer risk, which cancers are impacted either favorably or unfavorably, the role of the NIH and other research agencies, and key questions to address that will help us to move the science forward.

Long‐term cancer outcomes after bariatric surgery

“…Bariatric surgery remains the most effective treatment for severe obesity, demonstrating long‐term weight loss [4], remitting chronic metabolic diseases [29], reducing cardiovascular‐related disorders [30], and decreasing incidence of obesity‐related cancers [9]. Furthermore, findings of reduced cancer incidence following bariatric surgery has launched mechanistic discovery underlying the benefits of bariatric surgery, including reductions in tumor initiation and progression, cellular inflammation, insulin resistance, steatosis, lipid peroxidation, and oxidative stress—all pathways of etiological relevance for cancer [4,8,10,31‐34]. Although our study did not explore mechanistic aspects of bariatric surgery with reduced cancer incidence, this study clearly identified sex‐related differences for reduced cancer incidence; when cancer risk was stratified by sex, only female surgery patients demonstrated significant lowering of cancer incidence compared with nonsurgical females.…”

Bariatric Surgery and Cancer Risk

“…In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans . Some of these potential mechanisms include increased insulin sensitivity, decreased inflammation, altered gut microbiome, epigenetic changes, decreased conversion to estrogen, and lower cell proliferation.…”

“…Some of these potential mechanisms include increased insulin sensitivity, decreased inflammation, altered gut microbiome, epigenetic changes, decreased conversion to estrogen, and lower cell proliferation. There is strong interest in conducting additional research, considering that the understanding of the mechanisms involved may help inform new targeted therapies to reduce the risk of obesity-associated cancer …”

“…In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans. 13 Some of these potential mechanisms include increased insulin sensitivity, decreased inflammation, altered gut microbiome, epigenetic changes, decreased conversion to estrogen, and lower cell proliferation. There is strong interest in conducting additional research, considering that the understanding of the mechanisms involved may help inform new targeted therapies to reduce the risk of obesity-associated cancer.…”

“…There is strong interest in conducting additional research, considering that the understanding of the mechanisms involved may help inform new targeted therapies to reduce the risk of obesity-associated cancer. 13 In summary, bariatric surgery appears to be associated with a decreased risk of incident cancer and cancer mortality. More work needs to be done through large, well-designed studies that would include data on cancer screening, data from tumor registries, more detailed individual patient data, and investigations of the basic mechanisms of effect.…”