Upper abdominal obesity, insulin resistance and breast cancer risk

Stoll, Basil A.

doi:10.1038/sj.ijo.0801998

Cited by 87 publications

(54 citation statements)

References 82 publications

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“…58 Aberrant insulin signaling, which leads to insulin resistance, hyperinsulinaemia and increased concentrations of endogenous estrogen and androgen, was linked to high breast cancer risk by clinical and experimental evidence. 59 The above mentioned functions confirmed the expression behavior of selected genes, in tumor samples of our study and in metanalysis results. A quite different situation was observed for the remaining upregulated gene, SLPI.…”

Section: Discussionsupporting

confidence: 61%

Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues

Cimino

Fuso

Sfiligoi

et al. 2008

Intl Journal of Cancer

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Gene expression profiles were studied by microarray analysis in 2 sets of archival breast cancer tissues from patients with distinct clinical outcome. Seventy-seven differentially expressed genes were identified when comparing 30 cases with relapse and 30 cases without relapse within 72 months from surgery. These genes had a specific ontological distribution and some of them have been linked to breast cancer in previous studies: AIB1, the two keratin genes KRT5 and KRT15, RAF1, WIF1 and MSH6. Seven out of 77 differentially expressed genes were selected and analyzed by qRT-PCR in 127 cases of breast cancer. The expression levels of 6 upregulated genes (CKMT1B, DDX21, PRKDC, PTPN1, SLPI, YWHAE) showed a significant association to both disease-free and overall survival. Multivariate analysis using the significant factors (i.e., estrogen receptor and lymph node status) as covariates confirmed the association with survival. There was no correlation between the expression level of these genes and other clinical parameters. In contrast, SERPINA3, the only downregulated gene examined, was not associated with survival, but correlated with steroid receptor status. An indirect validation of our genes was provided by calculating their association with survival in 3 publicly available microarray datasets. CKMT1B expression was an independent prognostic marker in all 3 datasets, whereas other genes confirmed their association with disease-free survival in at least 1 dataset. This work provides a novel set of genes that could be used as independent prognostic markers and potential drug targets for breast cancer. ' 2008 Wiley-Liss, Inc.Key words: breast cancer; gene expression; microarray analysis; prognosticThe heterogeneous nature of breast cancer reflects the complexity of the molecular alterations that underlie the development and progression of this disease and poses serious problems to clinical management, also due to the lack of reliable pathological or molecular markers.There are a number of major open questions, such as the evaluation of risk of distant metastasis in cases characterized by the presence of favorable indicators (negative axillary lymph nodes and/or positive estrogen receptors), the prediction of response to chemotherapy and/or antiestrogenic therapy and the prediction of metastases sites for high-risk cancers. Moreover, the principal molecular alterations leading to aggressive clinical behavior, representing potential therapeutic targets, still need to be identified in addition to the well-known factor ERBB2 and the estrogen receptor pathways.Molecular profiling using DNA microarrays have provided sound advancements in this field. The expression profile of gene clusters were useful in classifying breast tumors in biological subgroups with clinical relevance, 1 or in low-versus high-risk classes for relapse, 2-5 or to predict responsiveness to either hormonal-or chemo-therapy. 6,7 In a well-known study, van't Veer et al. addressed the risk of relapse in node-negative patients, 2 one of the most clinicall...

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Section: Discussionsupporting

confidence: 61%

Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues

Cimino

Fuso

Sfiligoi

et al. 2008

Intl Journal of Cancer

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“…The factor(s) can be adsorbed by charcoal, because charcoal fully eliminated the growth-promoting effect of the ACCM. It is known that adipocytes are able to produce estrogen, which promotes breast cancer cell growth (20,35). However, estrogen cannot account for the SMC growth-promoting effect because estrogen does not stimulate but inhibits SMC proliferation as shown by our previous study (7).…”

Section: Discussionmentioning

confidence: 97%

Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity

Barandier¹,

Montani²,

Yang³

2005

American Journal of Physiology-Heart and Circulatory Physiology

124

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Adipocytes and perivascular adipose tissue are emerging as regulators of vascular function. The effects of adipocytes and perivascular adipose tissue on human smooth muscle cell (SMC) proliferation were investigated. Conditioned medium was prepared from cultured premature and differentiated 3T3-L1 adipocytes and from periaortic adipose tissue from young (3 mo) and old (24 mo) Wistar-Kyoto (WKY) rats, lean and obese Zucker rats (3 mo), and WKY rats fed normal chow or a high-fat diet for 3 mo. Conditioned medium from differentiated (but not premature) adipocytes stimulated SMC proliferation, which was abolished by charcoal and proteinase K treatment but was resistant to heat, trypsin, or phospholipase B (to hydrolyze lysophosphatidic acid). Further experiments demonstrated that the growth factor(s) are hydrosoluble and present in the fraction of molecular mass >100 kDa. Moreover, conditioned medium from periaortic adipose tissue stimulated SMC proliferation, which was significantly enhanced in aged rats and in rats fed a high-fat diet but not in obese Zucker rats deficient in functional leptin receptors. In conclusion, mature adipocytes release hydrosoluble protein growth factor(s) with a molecular mass >100 kDa for SMCs. Perivascular adipose tissue stimulates SMC proliferation, which is enhanced in aged WKY and in high-fat, diet-induced obesity but not in leptin receptor-deficient obese Zucker rats. These adipocyte-derived growth factor(s) and the effect of perivascular adipose tissue may be involved in vascular disease associated with aging and obesity.

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“…The apparent differences in the association between adiponectin levels and breast cancer risk in pre-and postmenopausal periods need to be studied further. Indeed, previous epidemiological studies have shown an association of obesity and insulin resistance mainly with postmenopausal breast cancer (Stoll 2002, Michels et al 2003. Finding a significant inverse relationship between adiponectin and breast cancer risk among postmenopausal women in this and previous studies (Mantzoros et al 2004, Tworoger et al 2007 provides further support for the importance of adiponectin in the pathogenesis of malignancies associated with obesity-induced insulin resistance and hyperinsulinemia.…”

Section: Discussionmentioning

confidence: 99%

Anthropometric measures, plasma adiponectin, and breast cancer risk

Tian¹,

Chu²,

Wu³

et al. 2007

Endocr Relat Cancer

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Adiponectin is a peptide hormone secreted exclusively by adipocytes, and obesity is an established risk factor for breast cancer. We have, thus, evaluated the associations of anthropometric measures of adiposity and adiponectin with the development of breast cancer in a case-control study. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 244 incident cases with breast cancer, including 141 premenopausal and 103 postmenopausal cases, and 244 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2005. Plasma levels of adiponectin were measured by RIA. The relationship between anthropometric measures of adiposity and breast cancer risk was modified by menopausal status, with a significant increase in risk observed in postmenopausal but not premenopausal women. Moreover, a fairly robust inverse association of adiponectin with the risk was observed only in postmenopausal women (adjusted odds ratio (OR), 0.55; 95% confidence interval (CI), 0.23-0.97), but not in premenopausal women. Additionally, the plasma adiponectin levels tended to be inversely associated with estrogen receptor (ER)-positive (adjusted OR, 0.53; 95% CI, 0.27-0.98) but not ER-negative breast tumors. Furthermore, the associations of adiponectin with breast cancer risk overall and by menopausal and ER status remained after adjustment for obesity indices. These results suggest that adiponectin may have an independent role in breast carcinogenesis, particularly in the postmenopausal and ER-positive breast cancer risk.

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Upper abdominal obesity, insulin resistance and breast cancer risk

Cited by 87 publications

References 82 publications

Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues

Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues

Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity

Anthropometric measures, plasma adiponectin, and breast cancer risk

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