Obesity and breast cancer: status of leptin and adiponectin in pathological processes

Großmann, Matthias; Ray, Arunima; Nkhata, Katai J.; Malakhov, Dmitry A.; Rogozina, Olga P.; Doğan, Soner; Cleary, Margot P.

doi:10.1007/s10555-010-9252-1

Cited by 161 publications

(118 citation statements)

References 128 publications

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“…These data clearly signal that the dietary ratio of n-3:n-6 had an effect on adipose tissue function, a finding consistent with a number of reports. However, despite the fact that the mammary epithelium is imbedded in a subcutaneous fat pad and that leptin and adiponectin have been implicated in mammary carcinogenesis (45)(46)(47)(48)(49), no relationship was observed between the plasma concentration of these cytokines and mammary gland density. The effects of the 25:1 n-3:n-6 dietary ratio on leptin and adiponectin was confirmed in experiment 4 and was observed in the presence or absence of tamoxifen treatment ( Table 5).…”

Section: Discussionmentioning

confidence: 97%

Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat

Zhu

Jiang

McGinley

et al. 2011

Cancer Prevention Research

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This study investigated the effect of a broad range of dietary ratios of n-3:n-6 fatty acids on mammary gland density and mammary cancer risk. Cancer was induced in female rats by N-methyl-N-nitrosourea. Purified diet that provided 30% of dietary kilocalories from fat was formulated to contain ratios of n-3:n-6 fatty acids from 25:1 to 1:25. Mammary gland density was determined by digital analysis, fatty acids by gas chromatography/flame ionization detection, and other plasma analytes via ELISA. Mammary gland density was reduced dose dependently at n-3:n-6 ratios from 1:1 to 25:1 (r ¼ À0.477, P ¼ 0.038), with a 20.3% decrease of mammary gland density between n-3:n-6 of 1:1 versus 25:1, P < 0.001. Mammary carcinogenesis was inhibited in the absence or presence of tamoxifen (1 mg/kg diet) in a manner predicted by mammary gland density. Plasma n-3 fatty acid concentrations failed to increase above an n-3:n-6 ratio of 5:1, and changes in specific plasma n-3 or n-6 fatty acids were not predictive of mammary gland density or cancer inhibitory activity. A strong reciprocal effect of the n-3:n-6 ratio on plasma leptin (decreased, P ¼ 0.005) and adiponectin (increased, P < 0.001) was observed indicating adipose tissue function was modulated. However, neither cytokine was predictive of mammary gland density. Plasma insulin-like growth factor I (IGF-I) decreased with increasing dietary n-3:n-6 ratio (P ¼ 0.004) and was predictive of the changes in mammary gland density (r ¼ 0.362, P < 0.005). These findings indicate that (i) mammary gland density predicted the carcinogenic response, (ii) the n-3:n-6 ratio exerts effects in the presence or absence of hormonal regulation of carcinogenesis, and (iii) signaling pathways regulated by IGF-I are potential targets for further mechanistic investigation. Cancer Prev Res; 4(10); 1675-85. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 97%

Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat

Zhu

Jiang

McGinley

et al. 2011

Cancer Prevention Research

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“…Several possible mechanisms have been suggested: i) Obese people often have increased levels of insulin and insulin-like growth factor-1 in their blood, which may promote the development of tumors (Belardi et al, 2013), ii) Adipose tissue produces hormones, called adipokines such as leptine and adiponectine, that may stimulate angiogenesis, growth of malignant cells (Grossmann et al, 2010;Khan et al, 2013) and that may modulate anti-tumor immune response (Catalan et al, 2013) iii) Finally, obesity is associated with elevated levels of pro-inflammatory cytokines (Harvey et al, 2011) which generate a low grade chronic inflammatory state that may be involved on cancer development (Hanahan and Weinberg, 2011;Ferguson et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Breast Cancer in Tunisia: Association of Body Mass Index with Histopathological Aspects of Tumors

Bouguerra

Guissouma²,

Labidi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Previous studies have suggested a link between obesity and breast cancer (BC). However, there is no universal consensus, especially in population based studies. Because only few studies have been conducted on African women, we aimed here to assess the relationship between BMI at time of diagnosis and the BC histopathological features among Tunisian patients according to menopausal status using a hospital-based prospective cohort study. Materials and Methods: Clinical and pathological data were collected from 262 patients stratified on four groups according to their BMI. The relationship between BMI and histopathological features at diagnosis was analysed using univariate and multivariate analysis. Receiver-operating characteristic (ROC) curves were used to evaluate the performance of BMI in predicting of high tumor grade, in comparison to ki-67 index of proliferation. Results: Obesity was correlated with larger tumors, advanced grade and with ER-PRHer2+ BC subtype. An association of BMI with tumor size and tumor grade was observed in both premenopausal and postmenopausal women. Additionally, a significant association between BMI and ER+, ER+PR+Her2+ and ER-PR-Her2+ status was revealed for premenopausal patients, while only ER+PR+Her2+ was associated with BMI for postmenopausal women. Finally, our results showed that compared to Ki67 proliferation index, BMI is a useful prognostic marker of high grade BC tumors. Conclusions: These data are the first to show that in Tunisia obese women suffering from BC have significantly larger tumors and advanced tumor grade and that higher BMI might influence tumor characteristics and behavior.

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“…Risk of meningioma may also be influenced by the expression of sex hormones (3). Over the last decade, numerous types of tumors have been correlated with obesity, including colorectal and breast cancer, and uterus adenocarcinoma (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…Leptin is a hormone synthesized by fatty tissue, and is responsible for the regulation of physiological processes, such as the modulation of appetite and thermogenesis, as well as pathological processes (9). A number of studies have demonstrated that the expression of the leptin receptor (LEPR, also known as ObR) correlates with the presence of leptin, suggesting that leptin-dependent malignancy may be regulated through autocrine and paracrine mechanisms (5,9). Leptin receptor isoforms are expressed throughout the central nervous system and a number of peripheral tissues, and six isoforms have been described previously.…”

Section: Introductionmentioning

confidence: 99%

“…Leptin receptor isoforms are expressed throughout the central nervous system and a number of peripheral tissues, and six isoforms have been described previously. All LEPRs belong to the cytokine receptor family, which signal through janus kinases (JAKs) and signal transducers and activators of transcription (STAT) (5,9,12). Overexpression of leptin and leptin receptor has been demonstrated previously in human cancers, including breast, colorectal, endometrial and prostate (9,12).…”

Section: Introductionmentioning

confidence: 99%

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Correlation of leptin receptor expression with BMI in differential grades of human meningiomas

Rutkowski¹,

Reszeć²,

Hermanowicz³

et al. 2016

Oncology Letters

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Abstract. Meningioma is one of the most common primary brain tumor, especially in postmenopausal women. The most important risk factors include radiation, primary head injury or genetic alterations, however it is currently unclear why postmenopausal women are predominantly affected. The aim of the present study was to evaluate leptin receptor (LEPR) expression and body mass index (BMI) in patients with meningiomas of differential grades. Specimens of 158 meningiomas were classified as either G1 (low-grade meningiomas, n=114) or G2/G3 (high-grade meningiomas, n=44). Immunohistochemistry was performed to assess LEPR expression. The mean BMIs of the female and male patient groups were 28.43±5.29 and 23.93±4.66, respectively. Mean BMI was significantly higher in the female group, by ~4.50 kg/m 2 . Patient age significantly correlated with LEPR expression, with the highly positive (++) and positive (+) groups having mean ages of 62.3±12.07 and 52.3±13.04, respectively. A strong positive correlation (r=0.73) was observed between leptin receptor expression and BMI, with the LEPR (++) group having a mean BMI of 30.11±4.49, compared to 22.12±2.48 for the LEPR (+) group. Furthermore, in the low-grade meningioma group, mean BMI was higher in female patients than male patients (28.13±5.54 and 25.38±4.57, respectively; P=0.01). Additionally, there was strong positive correlation between BMI and leptin receptor expression in the low-grade meningioma group (r=0.69). For the high-grade meningioma group, mean BMI was 29.49±4.26 and 21.76±3.98 in female and male patients, respectively, and LEPR expression strongly correlated with BMI in this group (r=0.80). The present study demonstrates a correlation between patient BMI, age, and LEPR expression status in low-and high-grade meningiomas. Our results indicate that in addition to endogenous hormones, such as estrogen or progesterone, or fatty tissue-associated proinflammatory cytokines, LEPR expression status may be a risk factor for meningioma growth and progression.

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Obesity and breast cancer: status of leptin and adiponectin in pathological processes

Cited by 161 publications

References 128 publications

Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat

Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat

Breast Cancer in Tunisia: Association of Body Mass Index with Histopathological Aspects of Tumors

Correlation of leptin receptor expression with BMI in differential grades of human meningiomas

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