Adiponectin gene and risk of colorectal cancer
ABSTRACT Genes of the adiponectin pathway are interesting candidates for colorectal cancer risk based on the potential association between colorectal cancer and obesity. However, variants of the adiponectin gene (ADIPOQ) have been demonstrated to be inconsistently associated with risk of colorectal cancer.
The current study attempted to evaluate these findings by examining several single nucleotide polymorphisms (SNPs) that were previously genotyped as part of a genome-wide association study in the ADIPOQ gene. Genotyping was also performed for a previously reported risk variant, rs266729, in 1062 individuals with a diagnosis of colorectal cancer and 1062 controls matched on age, gender and ethnicity (Jewish or not Jewish) as part of a population-based case-control study in Israel.
No evidence was found for an association between ADIPOQ and risk of colorectal cancer. The single nucleotide variant previously associated with decreased risk of colorectal cancer, rs266729, revealed an adjusted odds ratio of 1.04; 95% confidence interval, 0.88-1.23.
The SNP, rs266729, was not strongly associated with colorectal cancer in patients of Ashkenazi Jewish descent or other ethnic groups in Israel.
Full-textDOI: · Available from: Michele C Gornick, Sep 28, 2015
- SourceAvailable from: Krasimira Aleksandrova
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- "These data suggest that adiponectin is inversely associated with risk of colorectal cancer and that this association is largely accounted for by non-HMW-adiponectin. Studies that investigated the association between genetic variants at the adiponectin locus and the risk of colorectal cancer reported conflicting results; some studies showed significant associations [84, 85], whereas other studies did not observe any association . "
ABSTRACT: Obesity and related metabolic alterations have been implicated to play a role in colorectal cancer risk. The metabolic syndrome, as assessed according to current international definitions by the key components, abdominal obesity, dyslipidemia, elevated blood pressure, and abnormal glucose metabolism, is associated with colorectal cancer. Recent studies suggest that abdominal obesity and abnormal glucose metabolism may primarily account for this association. Visceral adipose tissue is physiologically more active than subcutaneous adipose tissue and generates hormones and cytokines with inflammatory, metabolic, and direct carcinogenic potential, which may directly or indirectly increase colorectal cancer risk. Current evidence suggests that obesity acts as a risk factor for colorectal cancer by several mechanisms, including chronic low-grade inflammation, hyperinsulinemia, as well as alterations in insulin-like growth factor and adipokine concentrations. Metabolic biomarkers reflecting these processes may not only provide clues for etiological understanding of colorectal carcinogenesis but also might be an alternative way to define an "obesity phenotype" that is relevant for colorectal cancer development.03/2013; 2(1):1-9. DOI:10.1007/s13668-012-0036-9
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ABSTRACT: 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. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.Endocrine reviews 04/2012; 33(4):547-94. DOI:10.1210/er.2011-1015 · 21.06 Impact Factor
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ABSTRACT: Adiponectin is an adipose tissue-derived hormone, expressed almost exclusively in adipose tissue, with significant anti-diabetic, anti-atherosclerotic, anti-inflammatory and anti-proliferative properties. The anti-carcinogenic effects of adiponectin result from two main mechanisms: a modulation in the signaling pathways involved in proliferation process and a subtle regulation of the apoptotic response. In this review, we present recent findings on the association of adiponectin with the risk of several malignancies (breast, colorectal, liver and prostate cancers), as well as data on underlying molecular mechanisms by which adiponectin plays a substantial role in cancer pathogenesis.Current Medicinal Chemistry 08/2012; 19(32). DOI:10.2174/092986712803833137 · 3.85 Impact Factor