The association of circulating adiponectin levels with pancreatic cancer risk: A study within the prospective EPIC cohort (original) (raw)
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The Journal of Clinical Endocrinology and Metabolism, 2020
Introduction: Despite the beneficial cardiometabolic effects of adiponectin demonstrated in preclinical studies, paradoxically higher circulating adiponectin concentrations have been found in epidemiological studies to be associated with incident cardiovascular events, renal outcomes, and mortality in patients with diabetes. On the other hand, diabetes is also associated with an increased risk of cancer. Here, we investigated prospectively the association between circulating adiponectin concentrations and incident cancer using a cohort of exclusively individuals with type 2 diabetes. Materials and Methods: Baseline serum adiponectin concentrations were measured in 5658 participants recruited from the Hong Kong West Diabetes Registry. The associations of circulating adiponectin concentrations with incident cancer and cancer-related deaths were evaluated using multivariable Cox regression analysis, with hazard ratio (HR) for adiponectin referring to the respective risk per doubling of serum adiponectin concentration. Results: Over a median-follow up of 6.5 years, 7.53% and 3% of participants developed cancer and had cancer-related deaths, respectively. Serum adiponectin concentrations were significantly higher in those who had incident cancer (9.8 μg/mL vs 9.1 μg/mL, P < 0.001) and cancer-related deaths (11.5 μg/mL vs 9.3 μg/mL, P < 0.001) compared with those without. Moreover, in multivariable analyses, serum adiponectin concentration was independently associated with both incident cancer (hazard ratio, 1.19; 95% confidence interval, 1.05-1.35; P = 0.006) and cancer-related deaths (hazard ratio, 1.23; 95% confidence interval, 1.03-1.47; P = 0.024). Conclusions: Higher serum adiponectin concentration was independently associated with incident cancer and cancer-related deaths in type 2 diabetes, indicating that adiponectin paradox can be observed in another major diabetic complication in addition to cardiovascular and kidney diseases.
Comparison of adiponectin concentration between pancreatic cancer and colorectal cancer
Journal of gastrointestinal oncology, 2011
Adiponectin (ADP) is an adipocytokine secreted by the adipose tissue which can be a useful marker in oncogenesis. Preliminary studies suggest that adiponectin rates differ according to the type of cancer. Compare ADP plasma levels in pancreatic cancer (PC) and colorectal cancer (CRC) in a prospective monocentric study. The study included all the incident cases of PC gathered from a university hospital in France from January 2006 till September 2007. A control population of incident cases of colorectal cancer (CRC), matching on age, gender, and tumor staging was set in the same period. In addition to demographic data, the other parameters analyzed were: ADP rate, insulinoresistance (Homa-test), presence of a dysmetabolic syndrome, evolution of weight and data concerning the tumor (staging, tumor markers: ACE, CA19.9). 33 CRC and 53 PC were analyzed. Type 2 diabetes was found in 18.2% of the CRC cases and 39.6% of the PC (p = 0.037). The mean ADP level was significantly higher in PC v...
Cancer causes & control : CCC, 2009
Obesity and insulin resistance have been implicated in the etiology of pancreatic cancer (PC). Whether adiponectin and/or leptin, two adipocyte-secreted hormones important in metabolic regulation, are associated with PC pathogenesis and whether adiponectin receptors are expressed in PC remains unknown. In a hospital-based case–control study, we studied 81 cases with incident, histologically confirmed PC and 81 controls matched on gender and age between 2000 and 2007 to investigate the role of adiponectin and leptin adjusting for risk factors linked to PC. In a separate study, we also studied for the first time whether adiponectin receptors 1 and 2 are expressed in PC by studying 16 PC tumor tissue samples which were analyzed using immunohistochemistry. When subjects were divided into control-defined quartiles of adiponectin and leptin, lower leptin but higher adiponectin levels were associated with PC (p = 0.001 and p = 0.05 respectively) before and after controlling for age, gender, BMI, smoking status, alcohol consumption, history of diabetes, and family history of pancreatic cancer. Of the PC tumor tissue samples analyzed, 87.5% had positive or strong positive expression of AdipoR1 and 93.7% had positive or strong positive expression of AdipoR2. Further prospective studies are needed to determine whether the elevated adiponectin and low leptin levels reported in this study reflect compensatory changes during PC progression and thus can be used as markers for PC or whether they are causally implicated in PC.
Low adiponectin levels are associated with renal cell carcinoma: A case-control study
International Journal of Cancer, 2007
Adiponectin is a novel endogenous insulin sensitizer, secreted by mature adipocytes. Circulating levels of adiponectin are inversely associated with obesity and insulin resistance. Because obesity is a risk factor for renal cell carcinoma (RCC), we hypothesized that low adiponectin levels are associated with RCC. To evaluate this hypothesis, we conducted a case-control study of 70 patients with histologically confirmed RCC and 280 healthy controls matched by gender, age and county of residence. Study subjects were interviewed and blood samples were collected during a 32-month period in Athens, Greece. Serum adiponectin levels were statistically, significantly and inversely associated with RCC when compared with controls (OR 5 0.76, p 5 0.05) and this association remained practically unchanged after controlling for BMI; the introduction of waist to hip ratio along with adiponectin in the multiple logistic regression analysis model rendered the association between adiponectin and RCC risk insignificant, indicating that altered levels of adiponectin may mediate the effect of central or intra-abdominal obesity on RCC. Prospective studies as well as studies exploring underlying mechanisms are needed to fully explore the role of adiponectin in predicting future risk of RCC in humans. ' 2006 Wiley-Liss, Inc.
Adiponectin and cancer: A systematic review
British Journal of Cancer, 2006
Recent studies have demonstrated that obesity is a significant risk factor for the development of several malignancies, but the mechanisms underlying this relationship remain to be fully elucidated. Adiponectin, an adipocyte secreted endogenous insulin sensitizer, appears to play an important role not only in glucose and lipid metabolism but also in the development and progression of several obesity-related malignancies. In this review, we present recent findings on the association of adiponectin with several malignancies as well as recent data on underlying molecular mechanisms that provide novel insights into the association between obesity and cancer risk. We also identify important research questions that remain unanswered.
Adiponectin as Link Factor between Adipose Tissue and Cancer
International Journal of Molecular Sciences
Adipose tissue is a key regulator of energy balance playing an active role in lipid storage as well as in synthesizing several hormones directly involved in the pathogenesis of obesity. Obesity represents a peculiar risk factor for a growing list of cancers and is frequently associated to poor clinical outcome. The mechanism linking obesity and cancer is not completely understood, but, amongst the major players, there are both chronic low-grade inflammation and deregulation of adipokines secretion. In obesity, the adipose tissue is pervaded by an abnormal number of immune cells that create an inflammatory environment supporting tumor cell proliferation and invasion. Adiponectin (APN), the most abundant adipokine, shows anti-inflammatory, anti-proliferative and pro-apoptotic properties. Circulating levels of APN are drastically decreased in obesity, suggesting that APN may represent the link factor between obesity and cancer risk. The present review describes the recent advances on t...
Linking Obesity and Pancreatic Cancer
Pancreatic Cancer - Insights into Molecular Mechanisms and Novel Approaches to Early Detection and Treatment, 2014
Additional information is available at the end of the chapter http://dx.doi.org/10.5772/58546
The Role of Adiponectin in Cancer: A Review of Current Evidence
Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents.