Circulating adipokines and risk of obesity related cancers: A systematic review and meta-analysis

Yoon, Yeong Sook; Kwon, A-Rom; Lee, Yoon Kyung; Oh, Sang Woo

doi:10.1016/j.orcp.2019.03.006

Cited by 87 publications

(79 citation statements)

References 112 publications

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“…Some studies suggested high levels of serum leptin as a biomarker for breast cancer development [27,28]. Since we determined no significant difference in serum leptin levels between MT-positive and MT-negative mice, our results are in accordance with the previous studies reporting no correlation between serum leptin levels and breast cancer development [14,16,25].…”

Section: Discussionsupporting

confidence: 92%

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Leptin Signaling in Liver Tissue of a Transgenic Breast Cancer Mouse Model

Tuna¹,

Cleary²,

Demirel³

et al. 2020

Cureus

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Leptin, an adipocytokine, is secreted from various tissues including the liver. The roles of both leptin and leptin receptor (ObR) in numerous pathophysiological conditions including mammary tumor (MT) development have been reported. However, the roles of leptin signalingrelated proteins in the liver have not been reported previously in MT development. The objective of this study was to examine the expression levels of leptin and ObR in liver tissue of a transgenic breast cancer mouse model to investigate whether the roles of leptin in MT development are systemic or local. MMTV-TGF-α transgenic female mice were fed ad-libitum from week 10 up to week 74. Protein expression levels of leptin and ObR were measured in liver tissues of 74-week-old MMTV-TGF-α mice with and without MT by western blot. Serum leptin and insulin levels were measured using a enzyme-linked immunosorbent assay. Protein expression levels of leptin and ObR were similar in mice with MT compared to the ones without MT. Serum leptin and insulin levels were also not significantly different between the two groups. These results indicate that the effects of leptin signaling in MT development might be important at a local tissue level, such as mammary fat pad, and not as important at a systemic level.

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Section: Discussionsupporting

confidence: 92%

“…Studies investigating the association between serum leptin levels and breast cancer revealed conflicting results: some studies reported a positive correlation between serum leptin levels and breast cancer risk, while others found either no association or a negative association [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Leptin Signaling in Liver Tissue of a Transgenic Breast Cancer Mouse Model

Tuna¹,

Cleary²,

Demirel³

et al. 2020

Cureus

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“…While not the focus of the present analysis, our next steps will be to examine other anthropometric measures (e.g., waist circumference, hip circumference, waist-to-hip ratio), as well as body composition measures (percent body fat), as predictors of adipokine expression in the tumor microenvironment, with consideration to differences by ER status. While numerous epidemiologic studies have explored and confirmed significant associations between circulating levels of the adipokines with risk of obesity-related cancers [48], fewer studies have examined the associations of IHC expression of the adipokines and their receptors with breast cancer clinicopathology [49][50][51][52][53][54][55][56][57], and most studies to date have been conducted in predominantly non-Black study samples. Findings from some of these studies suggest that LEPR expression might be downregulated in invasive tumors [50,55] (and those with more aggressive features, including TN subtypes and unfavorable Ki67 status [52]) as compared to DCIS and normal-adjacent tissues.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of adipokine and adipokine receptor expression in the breast tumor microenvironment: associations of lower leptin receptor expression with estrogen receptor-negative status and triple-negative subtype

et al. 2020

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Background: The molecular mechanisms underlying the association between increased adiposity and aggressive breast cancer phenotypes remain unclear, but likely involve the adipokines, leptin (LEP) and adiponectin (ADIPOQ), and their receptors (LEPR, ADIPOR1, ADIPOR2). Methods:We used immunohistochemistry (IHC) to assess LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 expression in breast tumor tissue microarrays among a sample of 720 women recently diagnosed with breast cancer (540 of whom self-identified as Black). We scored IHC expression quantitatively, using digital pathology analysis. We abstracted data on tumor grade, tumor size, tumor stage, lymph node status, Ki67, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) from pathology records, and used ER, PR, and HER2 expression data to classify breast cancer subtype. We used multivariable mixed effects models to estimate associations of IHC expression with tumor clinicopathology, in the overall sample and separately among Blacks. Results: Larger proportions of Black than White women were overweight or obese and had more aggressive tumor features. Older age, Black race, postmenopausal status, and higher body mass index were associated with higher LEPR IHC expression. In multivariable models, lower LEPR IHC expression was associated with ER-negative status and triple-negative subtype (P < 0.0001) in the overall sample and among Black women only. LEP, ADIPOQ, ADIPOR1, and ADIPOR2 IHC expression were not significantly associated with breast tumor clinicopathology. Conclusions: Lower LEPR IHC expression within the breast tumor microenvironment might contribute mechanistically to inter-individual variation in aggressive breast cancer clinicopathology, particularly ER-negative status and triple-negative subtype.

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“…By dose-response, we were able to more clearly explore the association between AdipoQ and leptin and the risk of HCC. In 2019, Yoon et al [60] found that AdipoQ levels were signi cantly associated with decreased risk of cancer, such as breast, colorectal, and endometrial cancer, and leptin was signi cantly associated with increased risk of cancer, such as endometrial and kidney cancer. However, our results showed that the increase of AdipoQ levels was signi cant for increasing HCC risk.…”

Section: Discussionmentioning

confidence: 99%

Association of Circulating Leptin and Adiponectin with Risk and Prognosis of Hepatocellular carcinoma: A Combination of Traditional, Survival and Dose-response Meta-analysis

Li-long

Yuan

et al. 2020

Preprint

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Background: The association between leptin, adiponectin levels and the risk and prognosis of hepatocellular carcinoma has been investigated by a growing number of studies, but the results were controversial. Methods: We performed the meta-analysis to assess the relationships between leptin, adiponectin levels and the risk and prognosis of hepatocellular carcinoma (CRD42020195882). Through June 14, 2020, PubMed, Cochrane Library, Embase databases, Clinicaltrials, and Opengrey was searhed, including references of qualifying articles. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Stata 16.0 was used to calculate statistical data. Results: Thirty studies were included in this meta-analysis and results showed that hepatocellular carcinoma group has significantly higher leptin levels than the cancer-free control group (SMD = 1.83, 95% CI (1.09, 2.58), P = 0.000) , the healthy control group (SMD = 4.32, 95% CI (2.41, 6.24), P = 0.000) and the cirrhosis group (SMD = 1.85, 95% CI (0.70, 3.01), P = 0.002). Hepatocellular carcinoma group has significantly higher adiponectin levels than the the healthy control group (SMD = 1.57, 95% CI (0.37, 2.76), P = 0.010), but no statistical difference compared with the cancer-free control group (SMD = 0.24, 95% CI (-0.35, 0.82), P = 0.430) and the cirrhosis group (SMD = -0.51, 95% CI (-1.30, 0.29), P= 0.213). The leptin rs7799039 polymorphism was associated with an increased the risk of hepatocellular carcinoma (G vs A: OR = 1.28, 95% CI (1.10, 1.48), P = 0.002). There were linear relationships between adiponectin levels and the risk of hepatocellular carcinoma (OR = 1.066, 95% CI (1.03, 1.11), P = 0.001). In addition, the results showed that high/positive expression of adiponectin was significantly related to lower overall survival in hepatocellular carcinoma patients (HR = 1.70, 95% CI (1.22, 2.37), P = 0.002); however, there was no significantly association between the leptin levels and overall survival (HR = 0.92, 95% CI (0.53, 1.59), P = 0.766). Conclusion: The study shows that high leptin levels were associated with a higher risk of hepatocellular carcinoma. Adiponectin levels were proportional to hepatocellular carcinoma risk, and were related to the poor prognosis.

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Circulating adipokines and risk of obesity related cancers: A systematic review and meta-analysis

Cited by 87 publications

References 112 publications

Leptin Signaling in Liver Tissue of a Transgenic Breast Cancer Mouse Model

Leptin Signaling in Liver Tissue of a Transgenic Breast Cancer Mouse Model

Immunohistochemical analysis of adipokine and adipokine receptor expression in the breast tumor microenvironment: associations of lower leptin receptor expression with estrogen receptor-negative status and triple-negative subtype

Association of Circulating Leptin and Adiponectin with Risk and Prognosis of Hepatocellular carcinoma: A Combination of Traditional, Survival and Dose-response Meta-analysis

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