Cancer in Obese Women: Potential Protective Impact of Bariatric Surgery

McCawley, Gwyneth M.; Ferriss, J. Stuart; Geffel, Dyanna L.; Northup, C. Joe; Modesitt, Susan C.

doi:10.1016/j.jamcollsurg.2009.01.045

Cited by 90 publications

(64 citation statements)

References 16 publications

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“…Data, recently been published from the Swedish Obesity Study [45], a prospective controlled interventional trial and with greater than 10 years median follow-up, show that bariatric surgery is associated with a reduced risk of developing cancers. Similar findings are also seen in three retrospective North American cohorts [46][47][48]. Interestingly, the beneficial effects of bariatric surgery on cancer incidence reduction appear to be limited to women [49].…”

Section: Causation Is More Likely If Evidence Is Based On Randomised supporting

confidence: 77%

Body Mass Index and Cancer Risk: The Evidence for Causal Association~!2009-04-22~!2009-06-16~!2010-07-13~!

Renehan¹,

Egger²,

Zwahlen³

2010

TOOBESJ

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Increased body mass index (BMI), as an approximation of body adiposity, is a risk factor for developing several adult malignancies. To quantify these risks, we reported a comprehensive systematic review (Lancet 2008; 371: 569-78) of prospective observational studies determining associations between BMI and risk of incident cancer for 20 cancer types. We demonstrated that associations are: (i) sex-specific; (ii) exist for a wider range of malignancies than previously thought; and (iii) are broadly consistent across geographic populations. In the present paper, we tested these data against the Bradford-Hill criteria of causal association, and argue that the available data support strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence and probably analogy. However, the experimental evidence supporting reversibility is currently lacking, though indirect evidence from longitudinal data in cohort studies and long-term follow-up post-bariatric surgery is emerging. We additionally assessed these data against appropriate adjustment for available confounding factors; measurement error and study design; and residual confounding; and found lack of alternative explanations. We conclude that there is considerable evidence to support a causal association between BMI and risk for many cancer types, but in order to establish the role of weight control in cancer prevention, there is a need to develop trial frameworks in which to better test reversibility.

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Section: Causation Is More Likely If Evidence Is Based On Randomised supporting

confidence: 77%

Body Mass Index and Cancer Risk: The Evidence for Causal Association~!2009-04-22~!2009-06-16~!2010-07-13~!

Renehan¹,

Egger²,

Zwahlen³

2010

TOOBESJ

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“…McCawley et al retrospectively studied 4977 morbidly obese females, reporting a 38% decrease in the incidence of all cancers defined by the Virginia Cancer Registry. 55 This study demonstrated that both obese controls and surgical patients were younger at cancer diagnosis compared with the general population of the Virginia Cancer Registry and that metabolic surgical patients had the diagnosis of the majority cancers at a younger age than obese controls. Adams et al noted that although there was a significant decrease in both incidence and mortality for morbidly obese females compared with controls, there was no significant difference in either mortality or incidence of cancer for men undergoing surgery.…”

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confidence: 69%

Metabolic surgery and cancer

Ashrafian

Ahmed

Rowland

et al. 2010

Cancer

139

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The worldwide epidemic of obesity and the global incidence of cancer are both increasing. There is now epidemiological evidence to support a correlation between obesity, weight gain, and some cancers. Metabolic or bariatric surgery can provide sustained weight loss and reduced obesity-related mortality. These procedures can also improve the metabolic profile to decrease cardiovascular risk and resolve diabetes in morbidly obese patients. The operations offer several physiological steps, the so-called BRAVE effects: 1) bile flow alteration, 2) reduction of gastric size, 3) anatomical gut rearrangement and altered flow of nutrients, 4) vagal manipulation and 5) enteric gut hormone modulation. Metabolic operations are also associated with a significant reduction of cancer incidence and mortality. The cancer-protective role of metabolic surgery is strongest for female obesity-related tumors; however, the underlying mechanisms may involve both weight-dependent and weight-independent effects. These include the improvement of insulin resistance with attenuation of the metabolic syndrome as well as decreased oxidative stress and inflammation in addition to the beneficial modulation of sex steroids, gut hormones, cellular energetics, immune system, and adipokines. Elucidating the precise metabolic mechanisms of cancer prevention by metabolic surgery can increase our understanding of how obesity, diabetes, and metabolic syndrome are associated with cancer. It may also offer novel treatment strategies in the management of tumor generation and growth. Cancer 2011;117:1788-99. V C 2010 American Cancer Society.KEYWORDS: metabolic surgery, bariatric surgery, cancer, oncology.The worldwide epidemic of obesity and the global incidence of cancer are both increasing. According to the World Health Organization (WHO), obesity is rising by 30 million cases per year, 1 whereas the overall number of new cancer cases will increase by 300,000 cases per year.2 Both obesity and cancer contribute to increased worldwide mortality and healthcare costs. They are now both recognized as global healthcare concerns and have been the subject of worldwide calls to action. 3,4Several treatment strategies have been developed to decrease obesity; these include prevention, lifestyle, behavioral modification, and pharmacotherapy. The weight-loss effects of these strategies have only been marginally successful, 5 and, therefore, a surgical solution has been developed to provide consistent weight loss in severely obese patients. The operations initially titled ''bariatric procedures'' have demonstrated long-term weight loss at more than 15 years after surgery 6,7 ; however in addition, they achieve pronounced metabolic effects including diabetes resolution in the majority of morbidly obese patients. [8][9][10] As a result, these procedures are now considered as ''metabolic'' operations. 10-14The epidemiological association between obesity rates and cancer rates has come under increased scrutiny as there is now evidence to establish obesity as a significant...

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“…Obesity [body mass index (BMI) > 30 kg/m 2 ] is associated with increased incidence, risk of death, and lower age of diagnosis for endometrial cancer (5)(6)(7). Disorders associated with hyperglycemia (type 1 and 2 diabetes) also have increased risk of endometrial cancer, indicating that poor control of blood glucose may be an important contributor to the growth of these tumors in women (8,9).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Vulnerabilities in Endometrial Cancer

et al. 2014

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Women with metabolic disorders, including obesity and diabetes, have an increased risk of developing endometrial cancer. However, the metabolism of endometrial tumors themselves has been largely understudied. Comparing human endometrial tumors and cells with their nonmalignant counterparts, we found that upregulation of the glucose transporter GLUT6 was more closely associated with the cancer phenotype than other hallmark cancer genes, including hexokinase 2 and pyruvate kinase M2. Importantly, suppression of GLUT6 expression inhibited glycolysis and survival of endometrial cancer cells. Glycolysis and lipogenesis were also highly coupled with the cancer phenotype in patient samples and cells. To test whether targeting endometrial cancer metabolism could be exploited as a therapeutic strategy, we screened a panel of compounds known to target diverse metabolic pathways in endometrial cells. We identified that the glycolytic inhibitor, 3-bromopyruvate, is a powerful antagonist of lipogenesis through pyruvylation of CoA. We also provide evidence that 3-bromopyruvate promotes cell death via a necrotic mechanism that does not involve reactive oxygen species and that 3-bromopyruvate impaired the growth of endometrial cancer xenografts Cancer Res; 74(20); 5832-45. Ó2014 AACR.

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Cancer in Obese Women: Potential Protective Impact of Bariatric Surgery

Cited by 90 publications

References 16 publications

Body Mass Index and Cancer Risk: The Evidence for Causal Association~!2009-04-22~!2009-06-16~!2010-07-13~!

Body Mass Index and Cancer Risk: The Evidence for Causal Association~!2009-04-22~!2009-06-16~!2010-07-13~!

Metabolic surgery and cancer

Metabolic Vulnerabilities in Endometrial Cancer

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