Effects of Bariatric Surgery on Cancer Risk: Evidence from Meta-analysis

Zhang, Kui; Luo, Yupeng; Dai, Hao

doi:10.1007/s11695-019-04368-4

Cited by 65 publications

(65 citation statements)

References 55 publications

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“…It is interesting that the 15% Ki-67 drop observed after six months treatment with the LNG-IUS was similar to that observed after an average bariatric surgery-induced weight loss of 22kg at two months in women with class III obesity [9]. Bariatric surgery is known to reduce endometrial cancer risk [7,8,35], and although the mechanisms underlying risk reduction are not fully understood, it is thought that down-regulation of endometrial pro-proliferative signalling pathways could be important [9,36]. Ki-67 is only expressed by proliferating cells, a hallmark of cancer; indeed, Ki-67 is known to differentiate benign from malignant endometrium, with higher Ki-67 scores observed in high grade, advanced stage cancer and correlating with poor survival outcomes in this group [37].…”

Section: Discussionsupporting

confidence: 54%

PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study

Derbyshire

Allen

Gittins

et al. 2021

Cancer Prevention Research

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Obesity is the major aetiological driver for endometrial cancer. The levonorgestrel intrauterine system (LNG-IUS) reduces the risk of endometrial cancer and its precursor, atypical hyperplasia. We assessed feasibility and uptake of the LNG-IUS for primary prevention of endometrial cancer in high-risk women and its impact on endometrial tissue biomarkers. Women with class-III obesity (BMI>40kg/m 2) and histologically normal endometrium were invited to participate in a clinical trial of the LNG-IUS for endometrial protection. Recruitment, successful LNG-IUS insertion and adherence to trial procedures were recorded. We measured impact of the LNG-IUS on circulating biomarkers of endometrial cancer risk, endometrial proliferation (Ki-67, pAKT, PTEN), endometrial hormone receptor status (ER, PR), mental wellbeing and menstrual function. At six months, women chose to keep their LNG-IUS or have it removed. In total, 103 women were approached, 54 were offered a participant information sheet, 35 agreed to participate and 25 received a LNG-IUS. Their median age and BMI were 54 years (IQR 52,57) and 47kg/m 2 (IQR 44,51) respectively. Three women (3/35, 9%) were ineligible due to atypical hyperplasia/endometrial cancer on their baseline biopsy. The LNG-IUS was well tolerated and had a positive overall effect on bleeding patterns and mental wellbeing. The LNG-IUS was associated with endometrial morphological change, reduced Ki-67 and PR expression but circulating biomarkers of endometrial cancer risk were unchanged. All but one woman (96%) kept her LNG-IUS. The LNG-IUS appears to be acceptable to some women with class-III obesity for primary prevention of endometrial cancer, which could provide a strategy for a prevention trial.

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Section: Discussionsupporting

confidence: 54%

PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study

Derbyshire

Allen

Gittins

et al. 2021

Cancer Prevention Research

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“…From a recent meta-analysis, bariatric surgery-and associated physiologic and metabolic changes-significantly reduced all-cause mortality from cancer (~33%-60%). [117][118][119][120][121][122][123][124][125][126][127][128][129][130][131] Retrospective studies found bariatric surgery significantly reduced risk for preand postmenopausal BC as well as skin cancer (including melanoma). 123,132 Of note for subtype-specific BC, bariatric surgery led to a 64% reduced risk in premenopausal ER tumors like TNBC.…”

Section: Tnbcs Also Disproportionately Affect African American Andmentioning

confidence: 99%

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Sipe

Chaib

Pingili

et al. 2020

Immunological Reviews

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Bile acids (BAs) are known facilitators of nutrient absorption but recent paradigm shifts now recognize BAs as signaling molecules regulating both innate and adaptive immunity. Bile acids are synthesized from cholesterol in the liver with subsequent microbial modification and fermentation adding complexity to pool composition. Bile acids act on several receptors such as Farnesoid X Receptor and the G proteincoupled BA receptor 1 (TGR5). Interestingly, BA receptors (BARs) are expressed on immune cells and activation either by BAs or BAR agonists modulates innate and adaptive immune cell populations skewing their polarization toward a more tolerogenic anti-inflammatory phenotype. Intriguingly, recent evidence also suggests that BAs promote anti-tumor immune response through activation and recruitment of tumoricidal immune cells such as natural killer T cells. These exciting findings have redefined BA signaling in health and disease wherein they may suppress inflammation on the one hand, yet promote anti-tumor immunity on the other hand. In this review, we provide our readers with the most recent understanding of the interaction of BAs with the host microbiome, their effect on innate and adaptive immunity in health and disease with a special focus on obesity, bariatric surgery-induced weight loss, and immune checkpoint blockade in cancer. K E Y W O R D S bariatric surgery, immunometabolism, microbiome, mitochondria, obesity, tumor microenvironment | 221 SIPE Et al.

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“…As a result, circulating insulin levels are decreased, which decreases the risk of EC induced by excessive insulin (37). Additionally, the downregulation of circulating insulin levels is considered helpful in the control of body weight, and reductions in body weight have been suggested to inhibit the carcinogenesis of EC (38). This may be at least partly explained by downregulated levels of adipokines and inflammatory factors.…”

Section: Metformin Inhibits the Development Of Ec By Ameliorating Insmentioning

confidence: 99%

Therapeutic effect of metformin in the treatment of endometrial cancer (Review)

Gao

et al. 2020

Oncol Lett

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The present review aims at reviewing the role of metformin in the treatment of endometrial cancer (EC). According to the literature, excessive estrogen levels and insulin resistance are established risk factors of EC. As a traditional insulin sensitizer and newly discovered anticancer agent, metformin directly and indirectly inhibits the development of EC. The direct mechanisms of metformin include inhibition of the LKB1-AMP-activated protein kinase-mTOR, PI3K-Akt and insulin-like growth factor 1-related signaling pathways, which reduces the proliferation and promotes the apoptosis of EC cells. In the indirect mechanism, metformin increases the insulin sensitivity of body tissues and decreases circulating insulin levels. Decreased levels of insulin increase the blood levels of sex hormone binding globulin, which leads to reductions in circulating estrogen and androgens. The aforementioned findings suggest that metformin serves an important role in the treatment of EC. Increased understanding of the mechanism of metformin in EC may provide novel insights into the treatment of this malignancy.

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Effects of Bariatric Surgery on Cancer Risk: Evidence from Meta-analysis

Cited by 65 publications

References 55 publications

PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study

PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Therapeutic effect of metformin in the treatment of endometrial cancer (Review)

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