ADIPOQ; adiponectin, C1Q and collagen domain containing (3q27)

Gene Summary

Gene:ADIPOQ; adiponectin, C1Q and collagen domain containing
Summary:This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Updated:11 December, 2014


What does this gene/protein do?
Show (81)


What pathways are this gene/protein implicaed in?
- Visceral Fat Deposits and the Metabolic Syndrome BIOCARTA
- Adipocytokine signaling pathway KEGG
- PPAR signaling pathway KEGG
- Type II diabetes mellitus KEGG
Data from KEGG and BioCarta [BIOCARTA terms] via CGAP

Cancer Overview

Research Indicators

Publications Per Year (1989-2014)
Graph generated 11 December 2014 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Genetic Association Studies
  • Genetic Variation
  • Haplotypes
  • Cell Proliferation
  • Chromosomes, Human, Pair None
  • Breast Cancer
  • Models, Genetic
  • Genetic Predisposition
  • Risk Factors
  • Odds Ratio
  • Case-Control Studies
  • Acute Lymphocytic Leukaemia
  • Messenger RNA
  • Signal Transduction
  • Single Nucleotide Polymorphism
  • Software
  • Risk Assessment
  • Colorectal Cancer
  • Genome-Wide Association Study
  • Insulin Resistance
  • Asian Continental Ancestry Group
  • Prostate Cancer
  • Polymorphism
  • Subcutaneous Fat
  • Cancer Gene Expression Regulation
  • Body Mass Index
  • Adolescents
  • Reproductive Techniques, Assisted
  • Leptin
  • Resistin
  • Receptors, Leptin
  • Alleles
  • Genotype
  • Polycystic Ovary Syndrome
  • Adiponectin
  • Carcinoma
  • Obesity
  • Receptors, Adiponectin
  • Smoking
  • Insulin
Tag cloud generated 11 December, 2014 using data from PubMed, MeSH and CancerIndex

Notable (4)

Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Acute Lymphocytic Leukaemia (ALL)ADIPOQ and Acute Lymphocytic Leukaemia View Publications1
Colorectal CancerADIPOQ and Colorectal Cancer View Publications15
Prostate CancerADIPOQ and Prostate Cancer View Publications5
Breast CancerADIPOQ and Breast Cancer View Publications5

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Related Links

Latest Publications: ADIPOQ (cancer-related)

Vetvik KK, Sonerud T, Lindeberg M, et al.
Globular adiponectin and its downstream target genes are up-regulated locally in human colorectal tumors: ex vivo and in vitro studies.
Metabolism. 2014; 63(5):672-81 [PubMed] Related Publications
OBJECTIVE: Low plasma adiponectin levels are linked to obesity, insulin resistance, and the risk of several types of malignancy. Despite the decline in circulating adiponectin concentrations, the increase in the expression of adiponectin receptors AdipoR1 and AdipoR2 is greater in cancerous than in normal colonic tissue. The purpose of this study was to obtain new information regarding local adiponectin signaling in the pathogenesis of colorectal cancer (CRC).
METHODS: We characterized the expressions of adiponectin and several of its downstream targets in paired samples of tumor tissue and adjacent noncancerous mucosa in 60 surgical patients with colorectal adenocarcinomas.
RESULTS: Adiponectin was expressed in both colorectal tumors and the adjacent mucosa. The expressions of adiponectin mRNA and its globular protein variant (gAd), adiponectin receptor type 1 and 5' AMP-activated protein kinase (AMPK) mRNA were significantly higher in colorectal tumors than in the adjacent mucosa. This finding was accompanied by increased mRNA expression of genes encoding proteins involved in fatty-acid trafficking and oxidation. The potential interference between adiponectin stimulation and AMPK activation through AMPK1 was examined in an in vitro model with the aid of silencing-RNA experiments. Furthermore, AMPK mRNA expression on tumors was positively correlated with a more advanced tumor stage in the patients.
CONCLUSION: We propose that the globular adiponectin-AMPK pathway functions in an autocrine manner in colorectal tumors, explaining some of the beneficial changes in cellular oxidative capacity in tumors in favor of tumorigenesis.

Related: Colorectal (Bowel) Cancer

Zhang W, Wei D, Sun X, et al.
Family-based analysis of adiponectin gene polymorphisms in Chinese Han polycystic ovary syndrome.
Fertil Steril. 2014; 101(5):1419-23 [PubMed] Related Publications
OBJECTIVE: To study the association between two single-nucleotide polymorphisms (SNPs) variants (rs2241766 and rs1501299) of the adiponectin gene (ADIPOQ) and polycystic ovary syndrome (PCOS) in PCOS family trios.
DESIGN: Family-based study.
SETTING: University hospital.
PATIENT(S): A total of 224 unrelated PCOS probands, their biologic parents, and 204 control subjects.
INTERVENTION(S): Anthropometric, hormonal, and metabolic assessment; genotype detection.
MAIN OUTCOME MEASURE(S): Basic endocrine, serum fasting glucose (FG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels were measured. The transmission disequilibrium test (TDT) was used to analyze the association between two SNPs of ADIPOQ and PCOS.
RESULT(S): A significant positive association was detected between SNP rs1501299 and PCOS. Compared with AA genotype, AC and CC genotypes had increased risk for PCOS, and the difference remained significant after adjustment for age, body mass index, and testosterone (T). The levels of T, TG, HDL cholesterol, and FINS were significantly higher in obese PCOS patients. However, we failed to find significant overtransmission of the other SNP, rs2241766, from parents to PCOS offspring. The genotype frequencies of rs2241766 and rs1501299 were not different in obese and lean PCOS patients and their parents.
CONCLUSION(S): TDT confirms that SNP rs1501299 in the ADIPOQ is significantly associated with the risk of PCOS in the Chinese Han population. The present data may provide a basis for further studies of the role of the ADIPOQ in the etiology of PCOS.

Yang Z, Yang X, Xu J, et al.
Association between adiponectin receptor 1 gene polymorphism and insulin resistance in Chinese patients with polycystic ovary syndrome.
Gynecol Obstet Invest. 2014; 77(1):45-9 [PubMed] Related Publications
BACKGROUND/AIMS: Adiponectin receptor 1 (ADIPOR1) is an identified receptor for adiponectin, an adipocytokine with anti-inflammatory and insulin-sensitizing properties. The ADIPOR1 gene is a potential candidate gene in polycystic ovary syndrome (PCOS). The aim of this study is to assess the association between single-nucleotide polymorphism (SNP) rs1539355 in the ADIPOR1 gene and PCOS in Chinese women.
METHODS: 302 patients with PCOS and 312 healthy controls were included in this study. The ADIPOR1 genotype distribution was detected using the polymerase chain reaction melting temperature shift method.
RESULTS: The genotypic distributions of SNP rs1539355 did not differ in patients with PCOS compared to controls. However, the frequency of the G allele in the PCOS group was significantly higher than that in the control group (p = 0.037). Patients with the AG or GG genotype had a higher homeostasis model assessment for insulin resistance (HOMA-IR) (p < 0.05) compared to patients with the AA genotype. The fasting insulin levels in subjects with the GG genotype were significantly higher than those in patients with the AA genotype (p < 0.05).
CONCLUSION: SNP rs1539355 in the ADIPOR1 gene is associated with insulin resistance in Chinese PCOS patients.

Wang D, Zhu W, Li J, et al.
Serum concentrations of fibroblast growth factors 19 and 21 in women with gestational diabetes mellitus: association with insulin resistance, adiponectin, and polycystic ovary syndrome history.
PLoS One. 2013; 8(11):e81190 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Fibroblast growth factor 19 (FGF19) and FGF21 are considered to be novel adipokines that improve glucose tolerance and insulin sensitivity. In the current study, we investigated serum FGF19 and FGF21 levels in patients with gestational diabetes mellitus (GDM) and explored their relationships with anthropometric and endocrine parameters.
METHOD: Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in patients with GDM (n = 30) and healthy pregnant controls (n = 60) matched for maternal and gestational age. Serum FGF19 and FGF21 levels were correlated with anthropometric, metabolic, and endocrine parameters.
RESULTS: Circulating levels of FGF19 were significantly reduced in patients with GDM relative to healthy pregnant subjects, whereas FGF21 levels were increased in GDM patients. Serum FGF19 levels independently and inversely correlated with insulin resistance (increased homeostasis model assessment of insulin resistance, HOMA-IR) and were positively related to serum adiponectin in both groups. In contrast, serum FGF21 levels independently and positively correlated with insulin resistance and serum triglycerides and were inversely related to serum adiponectin. In addition, in the combined population of both groups, those women with preconception polycystic ovary syndrome (PCOS) history had the lowest levels of FGF19, which were significantly lower than those in GDM patients without PCOS history and those in controls without PCOS history.
CONCLUSIONS: Circulating FGF19 levels are reduced in GDM patients, in contrast with FGF21 levels. Both serum FGF19 and FGF21 levels are strongly related to insulin resistance and serum levels of adiponectin. Considering the different situation between FGF19 and FGF21, we suggest that reduced serum FGF19 levels could be involved in the pathophysiology of GDM, while increased serum FGF21 levels could be in a compensatory response to this disease.

Comim FV, Hardy K, Franks S
Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome.
PLoS One. 2013; 8(11):e80416 [PubMed] Free Access to Full Article Related Publications
Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS.

Yi N, Xu S, Lou XY, Mallick H
Multiple comparisons in genetic association studies: a hierarchical modeling approach.
Stat Appl Genet Mol Biol. 2014; 13(1):35-48 [PubMed] Related Publications
Multiple comparisons or multiple testing has been viewed as a thorny issue in genetic association studies aiming to detect disease-associated genetic variants from a large number of genotyped variants. We alleviate the problem of multiple comparisons by proposing a hierarchical modeling approach that is fundamentally different from the existing methods. The proposed hierarchical models simultaneously fit as many variables as possible and shrink unimportant effects towards zero. Thus, the hierarchical models yield more efficient estimates of parameters than the traditional methods that analyze genetic variants separately, and also coherently address the multiple comparisons problem due to largely reducing the effective number of genetic effects and the number of statistically "significant" effects. We develop a method for computing the effective number of genetic effects in hierarchical generalized linear models, and propose a new adjustment for multiple comparisons, the hierarchical Bonferroni correction, based on the effective number of genetic effects. Our approach not only increases the power to detect disease-associated variants but also controls the Type I error. We illustrate and evaluate our method with real and simulated data sets from genetic association studies. The method has been implemented in our freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/).

Related: Colorectal (Bowel) Cancer

Moon HS, Mantzoros CS
Adiponectin and metformin additively attenuate IL1β-induced malignant potential of colon cancer.
Endocr Relat Cancer. 2013; 20(6):849-59 [PubMed] Related Publications
Both adiponectin (AD) and metformin (Met) have been proposed to downregulate cell proliferation of colon cancer cells, but whether their effect might be additive has not been studied to date. Genetic studies in humans have suggested an important role for interleukin 1β (IL1β) in cancer pathogenesis. Direct evidence that IL1β contributes to the development of colon cancer has not yet been fully confirmed and no previous studies have evaluated how IL1β may interact with AD and/or Met to regulate malignant potential and intracellular signaling pathways in human and mouse colon cancer cells. We conducted in vitro studies using human (LoVo) and mouse (MCA38) colon cancer cell lines to evaluate whether AD and Met alone or in combination may antagonize IL1β-regulated malignant potential in human and mouse colon cancer cell lines. IL1β increased malignant potential and regulated the expression of tumor suppressor (p53) and cell cycle regulatory genes (p21, p27, and cyclin E2) in human and mouse colon cancer cell lines. These effects were reversed by co-administration of AD and/or Met and were additively altered by AD and Met in combination in a STAT3- and AMPK/LKB1-dependent manner. We also observed using fluorescence activated cell sorter analysis that IL1β-regulated cell cycle progression is altered by AD and Met alone or in combination. Our novel mechanistic studies provide evidence for an important role for IL1β in colon cancer and suggest that AD and/or Met might be useful agents in the management or chemoprevention of IL1β-induced colon carcinogenesis.

Related: Apoptosis

Fabian CJ, Kimler BF, Donnelly JE, et al.
Favorable modulation of benign breast tissue and serum risk biomarkers is associated with > 10 % weight loss in postmenopausal women.
Breast Cancer Res Treat. 2013; 142(1):119-32 [PubMed] Free Access to Full Article Related Publications
We conducted a phase II feasibility study of a 6-month behavioral weight loss intervention in postmenopausal overweight and obese women at increased risk for breast cancer and the effects of weight loss on anthropomorphic, blood, and benign breast tissue biomarkers. 67 women were screened by random peri-areolar fine-needle aspiration, 27 were registered and 24 participated in the interventional phase. The 24 biomarker evaluable women had a median baseline BMI of 34.2 kg/m(2) and lost a median of 11 % of their initial weight. Significant tissue biomarker modulation after the 6-month intervention was noted for Ki-67 (if restricted to the 15 women with any Ki-67 at baseline, p = 0.041), adiponectin to leptin ratio (p = 0.003); and cyclin B1 (p = 0.001), phosphorylated retinoblastoma (p = 0.005), and ribosomal S6 (p = 0.004) proteins. Favorable modulation for serum markers was observed for sex hormone-binding globulin (p < 0.001), bioavailable estradiol (p < 0.001), bioavailable testosterone (p = 0.033), insulin (p = 0.018), adiponectin (p = 0.001), leptin (p < 0.001), the adiponectin to leptin ratio (p < 0.001), C-reactive protein (p = 0.002), and hepatocyte growth factor (p = 0.011). When subdivided by <10 or >10 % weight loss, change in percent total body and android (visceral) fat, physical activity, and the majority of the serum and tissue biomarkers were significantly modulated only for women with >10 % weight loss from baseline. Some factors such as serum PAI-1 and breast tissue pS2 (estrogen-inducible gene) mRNA were not significantly modulated overall but were when considering only those with >10 % weight loss. In conclusion, a median weight loss of 11 % over 6 months resulted in favorable modulation of a number of anthropomorphic, breast tissue and serum risk and mechanistic markers. Weight loss of 10 % or more should likely be the goal for breast cancer risk reduction studies in obese women.

Related: Breast Cancer MKI67

Howe LR, Subbaramaiah K, Hudis CA, Dannenberg AJ
Molecular pathways: adipose inflammation as a mediator of obesity-associated cancer.
Clin Cancer Res. 2013; 19(22):6074-83 [PubMed] Free Access to Full Article Related Publications
The increasing rate of obesity worldwide is predicted to be associated with a surge in diseases. Notably, obesity has been linked to approximately 20% of cancer cases in the United States; obesity is associated with both increased risk and worse outcomes after diagnosis. Altered levels of circulating factors are strongly implicated, including insulin, insulin-like growth factor 1, leptin, adiponectin, and interleukin-6 (IL-6). In addition, increasing attention has focused on the consequences of local adipose inflammation. Inflammatory foci characterized by crown-like structures consisting of dead adipocytes encircled by macrophages occur in white adipose depots, including the breast tissue, of most overweight and obese women. Saturated fatty acids, released as a consequence of obesity-associated lipolysis, induce macrophage activation via Toll-like receptor 4, thereby stimulating NF-κB signaling. This, in turn, activates transcription of proinflammatory genes including COX-2, IL-6, IL-1β, and TNFα. Elevated levels of proinflammatory mediators cause both local and systemic effects. Of particular relevance with regard to breast cancer is increased transcription of the CYP19 gene encoding aromatase, the rate-limiting enzyme for estrogen synthesis. Notably, this obesity-inflammation-aromatase axis provides a plausible explanation for increased rates of postmenopausal, hormone receptor-positive breast cancer associated with obesity and hence may offer targets for interventions to attenuate risk or improve prognosis. Potential approaches include weight reduction, exercise, and suppression of obesity-driven signaling pathways using pharmaceutical or dietary agents. A key future goal is to identify biomarkers that accurately report adipose inflammation, both for identification of at-risk individuals and to assess the efficacy of interventions. Clin Cancer Res; 19(22); 6074-83. ©2013 AACR.

Related: Breast Cancer COX2 (PTGS2) TNF

Reddy SM, Sadim M, Li J, et al.
Clinical and genetic predictors of weight gain in patients diagnosed with breast cancer.
Br J Cancer. 2013; 109(4):872-81 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Post-diagnosis weight gain in breast cancer patients has been associated with increased cancer recurrence and mortality. Our study was designed to identify risk factors for this weight gain and create a predictive model to identify a high-risk population for targeted interventions.
METHODS: Chart review was conducted on 459 breast cancer patients from Northwestern Robert H. Lurie Cancer Centre to obtain weights and body mass indices (BMIs) over an 18-month period from diagnosis. We also recorded tumour characteristics, demographics, clinical factors, and treatment regimens. Blood samples were genotyped for 14 single-nucleotide polymorphisms (SNPs) in fat mass and obesity-associated protein (FTO) and adiponectin pathway genes (ADIPOQ and ADIPOR1).
RESULTS: In all, 56% of patients had >0.5 kg m(-2) increase in BMI from diagnosis to 18 months, with average BMI and weight gain of 1.9 kg m(-2) and 5.1 kg, respectively. Our best predictive model was a primarily SNP-based model incorporating all 14 FTO and adiponectin pathway SNPs studied, their epistatic interactions, and age and BMI at diagnosis, with area under receiver operating characteristic curve of 0.85 for 18-month weight gain.
CONCLUSION: We created a powerful risk prediction model that can identify breast cancer patients at high risk for weight gain.

Related: Breast Cancer

Chew SH, Okazaki Y, Nagai H, et al.
Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production.
Carcinogenesis. 2014; 35(1):164-72 [PubMed] Related Publications
Like many other human cancers, the development of malignant mesothelioma is closely associated with a chronic inflammatory condition. Both macrophages and mesothelial cells play crucial roles in the inflammatory response caused by asbestos exposure. Here, we show that adipocytes can also contribute to asbestos-induced inflammation through dysregulated adipocytokine production. 3T3-L1 preadipocytes were differentiated into mature adipocytes prior to use. These cells took up asbestos fibers (chrysotile, crocidolite and amosite) but were more resistant to asbestos-induced injury than macrophages and mesothelial cells. Expression microarray analysis followed by reverse transcription-PCR revealed that adipocytes respond directly to asbestos exposure with an increased production of proinflammatory adipocytokines [e.g. monocyte chemoattractant protein-1 (MCP-1)], whereas the production of anti-inflammatory adipocytokines (e.g. adiponectin) is suppressed. This was confirmed in epididymal fat pad of mice after intraperitoneal injection of asbestos fibers. Such dysregulated adipocytokine production favors the establishment of a proinflammatory environment. Furthermore, MCP-1 marginally promoted the growth of MeT-5A mesothelial cells and significantly enhanced the wound healing of Y-MESO-8A and Y-MESO-8D human mesothelioma cells. Our results suggest that increased levels of adipocytokines, such as MCP-1, can potentially contribute to the promotion of mesothelial carcinogenesis through the enhanced recruitment of inflammatory cells as well as a direct growth and migration stimulatory effect on mesothelial and mesothelioma cells. Taken together, our findings support a potential cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis.

Related: Lung Cancer Mesothelioma

Ye L, Zhang ZY, Du WD, et al.
Genetic analysis of ADIPOQ variants and gastric cancer risk: a hospital-based case-control study in China.
Med Oncol. 2013; 30(3):658 [PubMed] Related Publications
Single-nucleotide polymorphisms (SNPs) of adiponectin (ADIPOQ), adiponectin receptor 1 (ADIPOR1) and ADIPOR2 genes contribute to the risk and progression of cancers. Here, we investigated the associations between variants of these three genes and the risk of gastric cancer. We genotyped six ADIPOQ SNPs, nine ADIPOR1 SNPs and six ADIPOR2 SNPs using the Sequenom technique in a hospital-based case-control study of patients with gastric cancer and cancer-free controls in the Chinese Han population. We found associations of certain variants with location of gastric cancer. Rs16861205 with the minor allele A in ADIPOQ, rs10773989 with the minor allele C and rs1044471 with the minor allele T in ADIPOR2 presented significant associations with a decreased risk of cardia cancer (P = 0.024, OR 0.605, 95 % CI 0.390-0.938; P = 0.015, OR 0.699, 95 % CI 0.522-0.935; and P = 0.022, OR = 0.703, 95 % CI 0.519-0.951, respectively). ADIPOQ rs16861205 with minor allele A displayed an association with an increased risk of body cancer (P = 0.010, OR 1.821, 95 % CI 1.148-2.890). Further stratified analysis of the patients indicated that there were significant correlations for rs1342387A/G (P = 0.027) and rs16861205A/G (P = 0.000) with tumor location; rs16850799A/G (P = 0.004) and rs2058033C/A (P = 0.003) with invasion depth; rs16850799A/G (P = 0.019) with the tumor-node-metastasis stage; rs16850799A/G (P = 0.016), rs1501299A/C (P = 0.005) and rs1063538C/T (P = 0.017) with alcohol consumption; rs11612414A/G (P = 0.040) and rs12733285T/C (P = 0.005) with salted food; rs1063538C/T (P = 0.043) with family history of gastric cancer; and rs11612414A/G (P = 0.029) with gender. Adiponectin expression significantly correlated with gender (P = 0.014), alcohol consumption (P = 0.037), family history (P = 0.019) and invasion depth of primary tumor (P = 0.024). Our data suggested that variants of ADIPOQ may be genetic markers conferring susceptibility to gastric cancer subtypes. These findings need to be validated in a larger panel of samples from distinct populations.

Related: Stomach Cancer Gastric Cancer

Ntikoudi E, Kiagia M, Boura P, Syrigos KN
Hormones of adipose tissue and their biologic role in lung cancer.
Cancer Treat Rev. 2014; 40(1):22-30 [PubMed] Related Publications
INTRODUCTION: Adipose tissue secretes numerous bioactive peptides, collectively termed "adipocytokines" or "adipokines". Adipokines act in a paracrine, autocrine, or endocrine manner and regulate several physiological and pathological processes. Increasing evidence indicates that adipokines are implicated also in several malignancies, including lung cancer as well.
AIM: The aim of this study is to summarize data concerning adipokines in lung cancer pathogenesis, prognosis and survival; the role of adipokines in lung cancer cachexia is also examined.
MATERIALS AND METHODS: A systematic literature search was performed in the electronic database of Medline. Several studies and review articles met the inclusion criteria.
RESULTS: Leptin and adiponectin are the best studied adipokines. The majority of the relevant studies has investigated the potential correlations mainly between leptin, adiponectin, and sometimes also resistin, and nutritional status, systemic inflammation of lung cancer or lung cancer cachexia and have also assessed their prognostic significance. Few other studies have studied genetic variations in leptin, leptin receptor and adiponectin genes and their association with lung cancer susceptibility and prognosis. The ongoing list of adipokines associated with lung cancer also includes resistin, chemerin, and visfatin.
CONCLUSIONS: Increasing evidence points to the involvement of certain adipocytokines in lung cancer development, progression and prognosis. No conclusive evidence exists so far with regards to the role of adipocytokines in lung cancer cachexia. Future, longitudinal studies are warranted in order to clarify the role of adipocytokines in lung cancer and also uncover adipocytokines as novel therapeutic targets.

Related: Non-Small Cell Lung Cancer Lung Cancer

Ye C, Wang J, Tan S, et al.
Meta-analysis of adiponectin polymorphisms and colorectal cancer risk.
Int J Med Sci. 2013; 10(9):1113-20 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: The adiponectin gene (ADIPOQ) has been suggested to be associated with the pathogenesis of colorectal cancer (CRC). However, the results have been inconsistent. In this study, we performed a meta-analysis to investigate the association between adiponectin polymorphisms and CRC risk.
METHODS: All eligible case-control studies published up to March 2013 were identified by searching PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model.
RESULTS: A total of 9 case-control studies were included, Of those studies, there were eight studies (2024 cases and 2777 controls) for rs1501299G/T polymorphism, five studies (1401 cases and 1691 controls) for rs2241766T/G polymorphism, five studies (2945 cases and 3361 controls) for rs266729C/G polymorphism, three studies (1221 cases and 1579 controls) for rs822395A/C polymorphism and three studies (1222 cases and 1575 controls) for rs822396A/G polymorphism. Overall, a significant association was observed for rs2241766T/G polymorphism under heterozygote comparison (TG vs. TT: OR=1.22, 95%CI: 1.05-1.43); while there was no significant association for rs2241766 polymorphism under other genetic models, and for other four polymorphisms under all genetic models. Besides, when stratified analyses by ethnicity, no significant association between five polymorphisms and CRC risk were observed under all genetic models among Asian, Caucasian and African-American.
CONCLUSIONS: This meta-analysis indicated that adiponectin rs2241766T/G rather than rs1501299G/T, rs266729C/G, rs822395A/C and rs822396A/G polymorphism was associated with the risk of colorectal cancer.

Related: Colorectal (Bowel) Cancer Polymorphisms

Bochenek G, Häsler R, El Mokhtari NE, et al.
The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10.
Hum Mol Genet. 2013; 22(22):4516-27 [PubMed] Related Publications
The long non-coding RNA ANRIL is the best replicated genetic risk locus of coronary artery disease (CAD) and periodontitis (PD), and is independently associated with a variety of other immune-mediated and metabolic disorders and several forms of cancer. Recent studies showed a correlation of decreased concentrations of proximal ANRIL transcripts with homozygous carriership of the CAD and PD main risk alleles. To elucidate the relation of these transcripts to disease manifestation, we constructed a short hairpin RNA in a stable inducible knock-down system of T-Rex 293 HEK cell lines, specifically targeting the proximal transcripts EU741058 and DQ485454. By genome-wide expression profiling using Affymetrix HG1.0 ST Arrays, we identified the transcription of ADIPOR1, VAMP3 and C11ORF10 to be correlated with decreased ANRIL expression in a time-dependent manner. We validated these findings on a transcriptional and translational level in different cell types. Exploration of the identified genes for the presence of disease associated variants, using Affymetrix 500K genotyping and Illumina custom genotyping arrays, highlighted a region upstream of VAMP3 within CAMTA1 to be associated with increased risk of CAD [rs10864294 P = 0.015, odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.1-1.6, 1471 cases, 2737 controls] and aggressive PD (AgP; P = 0.008, OR = 1.31, 95% CI = 1.1-1.6, 864 cases, 3664 controls). In silico replication in a meta-analysis of 14 genome-wide association studies of CAD of the CARDIoGRAM Consortium identified rs2301462, located on the same haplotype block, as associated with P = 0.001 upon adjustment for sex and age. Our results give evidence that specific isoforms of ANRIL regulate key genes of glucose and fatty acid metabolism.

Related: Cancer Prevention and Risk Reduction RASSF7

Hwang MS, Yu N, Stinson SY, et al.
miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer.
PLoS One. 2013; 8(6):e66502 [PubMed] Free Access to Full Article Related Publications
The epithelial-to-mesenchymal transition (EMT) is a highly conserved physiological program involved in development and tissue repair; however, its aberrant activation has been implicated in accelerating the progression of a variety of cancers. In breast cancer, the microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) are differentially expressed in the clinically more aggressive basal-like subtype compared to luminal subtype of breast cancer and upregulation of miR-221/222 induces the EMT by targeting the 3' untranslated region (3'UTR) of the GATA family transcriptional repressor TRPS1 (tricho-rhino-phalangeal syndrome type 1). The complete mechanism through which miR-221/222 promotes the EMT, however, is not fully understood. We identified adiponectin receptor 1 (ADIPOR1), a receptor for the adipocytokine adiponectin, as a direct target of miR-221/222. ADIPOR1 is expressed at higher levels in the luminal compared to the basal-like subtype of breast cancer cell lines, which can be reduced by miR-221/222 targeting of its 3'UTR. In addition, miR-221/222 were negatively correlated with ADIPOR1 expression across breast cancer cell lines and tumors. ADIPOR1 depletion by siRNA in MCF10A cells induced the EMT and increased cell invasion. Depletion of ADIPOR1 by siRNA induced activation of the canonical nuclear factor-kappaB (NF-κB) and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) in an interleukin 6 (IL6)-dependent manner. Finally, overexpression of ADIPOR1 in the basal-like cell line, MDA-MB-231, attenuated cell invasion and promoted the mesenchymal-to-epithelial transition (MET). We conclude that ADIPOR1 negatively regulates EMT in breast cancer and provides an additional node by which miR-221/222 induces the EMT. These results suggest that ADIPOR1 may play an important role in breast cancer progression and metastasis, and could potentially offer an alternative therapeutic strategy for basal-like breast cancer patients.

Related: Breast Cancer

Li L, Lee KJ, Choi BC, Baek KH
Relationship between leptin receptor and polycystic ovary syndrome.
Gene. 2013; 527(1):71-4 [PubMed] Related Publications
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, which is involved in the multi-system disease, and its etiology is still not clearly understood. It is currently considered that not only the genetic factors but also the environment factors play a crucial role in the pathogenesis of PCOS. Obesity plays an important role through the insulin, leptin and endocannabinoid system in the pathological process of PCOS, leading to more severe clinical manifestations. The aim of our present study is to investigate whether there is association between single nucleotide polymorphisms (SNPs) of Gln223Arg and Pro1019Pro in the leptin receptor gene (LEPR) and PCOS in a Korean population. Interestingly, a significant association was found between the Pro1019Pro in LEPR gene and PCOS, and a highly significant association was found between the Gln223Arg in LEPR gene and PCOS (P=0.033, OR=1.523, 95% confidence interval and P<0.0001, OR=0.446, 95% confidence interval). Moreover, genotype combination and haplotype analyses indicate that Gln223Arg and Pro1019Pro polymorphisms of LEPR are significantly associated with the risk of PCOS.

Mokrowiecka A, Sokolowska M, Luczak E, et al.
Adiponectin and leptin receptors expression in Barrett's esophagus and normal squamous epithelium in relation to central obesity status.
J Physiol Pharmacol. 2013; 64(2):193-9 [PubMed] Related Publications
UNLABELLED: Esophageal adenocarcinoma incidence is rapidly increasing which may be due to the growing incidence of Barrett's esophagus (BE) and obesity. The mechanisms linking obesity and progression of Barrett's carcinogenesis is poorly understood. The aim of the study was to evaluate the expression of adipokines receptors in BE and in normal squamous epithelium in the same patients in correlation with obesity parameters.
METHODS: Expression of adiponectin receptors 1 and 2 protein (AdipoR1, AdipoR2) as well as leptin receptor protein (ObR) in biopsies from 27 BE and normal squamous epithelium (N) in the same patients as well as in obese and normal controls were assessed with Western-blot analysis. These correlations were confirmed with the quantitative RT-PCR (qRT-PCR). AdipoR1 and ObR protein levels were similar in BE mucosa and squamous epithelium in the same patients in Western-blot analysis (2303 vs. 2448 OB units; 106927 vs. 103390, respectively; p>0.05). RT-PCR analysis confirmed this observation for AdipoR1, R2 and ObR genes expression (0.11±0.08 vs. 0.19±0.24, p=0.78; 0.24±0.36 vs. 0.33±0.49, p=0.5375; 0.71±0.8 vs. 1.33±2.95, p=1.0; respectively). Using linear correlation analysis we found the positive correlation between AdipoR1 expression in Barrett's epithelium compared to squamous epithelium in the same patients (N) (r=0.5; p=0.008) and between ObR expression in BE and N (r=0.8; p<0.001). The AdipoR1 and ObR protein levels were significantly higher in BE patients compared to controls and obese controls (2303 vs. 895 vs. 1674 and OD units, p<0.05).
CONCLUSIONS: in opposite to the prior hypothesis adiponectin and leptin receptors activation in BE may be not caused by obesity.

Related: Cancer of the Esophagus Esophageal Cancer

Delort L, Lequeux C, Dubois V, et al.
Reciprocal interactions between breast tumor and its adipose microenvironment based on a 3D adipose equivalent model.
PLoS One. 2013; 8(6):e66284 [PubMed] Free Access to Full Article Related Publications
Breast cancer has become the most common cancer among women in industrialized countries. Obesity is well established as a risk factor, in particular owing to the attendant secretion of the entities called adipokines; there is growing evidence for a role of cells and factors present in the mammary tumor microenvironment such as fibroblasts, preadipocytes, adipocytes and their secretions. To study how the microenvironment influences breast cancer growth, we developed a novel tridimensional adipose model epithelialized with normal human keratinocytes or with breast cancer cell lines. These mimicked a breast tumor in contact with an adipose microenvironment and allowed monitoring of the interactions between the cells. Leptin and adiponectin, two major adipokines, and their respective receptors, ObRt and AdipoR1, were expressed in the model, but not the second adiponectin receptor, AdipoR2. The differentiation of preadipocytes into adipocytes was greater when they were in contact with the breast cancer cell lines. The contact of breast cancer cell lines with the microenvironment completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal pathways (ESR1, IL6). This tridimensional adipose model provides new insights into the interactions between breast cancer cells and their adipose microenvironment, and provides a tool to develop new drugs for the treatment of both cancer and obesity.

Related: Breast Cancer

Cai X, Gan Y, Fan Y, et al.
The adiponectin gene single-nucleotide polymorphism rs1501299 is associated with hepatocellular carcinoma risk.
Clin Transl Oncol. 2014; 16(2):166-72 [PubMed] Related Publications
PURPOSE: Increasing lines of evidence have suggested that adiponectin, an adipocyte-derived hormone, plays an important role in the development of hepatocellular carcinoma (HCC). However, the relationship between genetic variants of the adiponectin gene (ADIPOQ) and HCC has not been previously explored. Therefore, we performed a case-control study to examine the association of haplotype-tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ with HCC risk.
METHODS: Five haplotype-tagging SNPs of ADIPOQ (rs266729, rs822395, rs822396, rs2241766 and rs1501299) were genotyped in 200 HCC patients and 200 non-HCC controls by PCR amplification and direct sequencing. Logistic regression was used to estimate the risk of HCC associated with each individual SNP and we adjusted for multiple testing by the Bonferroni correction.
RESULTS: Of the five tested SNPs, rs1501299 showed a strong and significant association with HCC risk even after the Bonferroni correction. After adjusting for the serological status of the hepatitis virus B core antibody and for other SNPs, the odds ratios were 4.33 [95 % confidence interval (CI) 2.07-9.05; corrected P < 0.005] and 3.71 (95 % CI 1.84-7.48; corrected P < 0.005) for the GG genotype and GG/GT combined genotype, respectively, versus the TT genotype.
CONCLUSIONS: This is the first report, demonstrating an association of ADIPOQ polymorphisms with HCC risk. Our results implicate the ADIPOQ SNP rs1501299 as a susceptibility locus for HCC.

Related: Liver Cancer

Radavelli-Bagatini S, de Oliveira IO, Ramos RB, et al.
Haplotype TGTG from SNP 45T/G and 276G/T of the adiponectin gene contributes to risk of polycystic ovary syndrome.
J Endocrinol Invest. 2013 Jul-Aug; 36(7):497-502 [PubMed] Related Publications
BACKGROUND: Haplotypes of adiponectin gene single nucleotide polymorphisms (SNP) might be related to metabolic disorders.
AIM: To assess whether the prevalence of SNP 45T/G and 276G/T of the adiponectin gene and their haplotypes differ between polycystic ovary syndrome (PCOS) and non-hirsute cycling controls and to investigate the relationship between these haplotypes and risk factors for cardiovascular disease.
SUBJECTS AND METHODS: In this case-control study, 80 women with PCOS and 1500 non-hirsute controls with regular cycles underwent clinical and laboratory measurements. Genotype distribution was analyzed by conventional PCR-restriction fragment length polymorphism.
RESULTS: Compared to controls, PCOS women had greater body mass index (BMI) (31.0±7.9 kg/m² vs 23.4±4.6 kg/m²; p<0.001), waist circumference (92.2±18.8 cm vs 74.5±10.2 cm; p<0.001), and systolic and diastolic blood pressure (124.6±19.9 vs 111.5±13.0 mmHg and 79.2±12.5 vs 71.8±10.6 mmHg; p<0.025), as well as a worse lipid profile (p<0.007), even after adjustment for age and BMI. Genotype distribution was similar in PCOS and controls (45T/G: p=0.399; 276G/T: p=0.135). Six haplotypes were inferred and their frequencies differed significantly between the groups (p=0.001). The TGTG haplotype was more frequent in PCOS than controls (41.3 vs 18.9%). In PCOS, the GG genotype for SNP 276 (p=0.031) and the TGTG haplotype (p=0.023) were associated with higher systolic blood pressure vs other genotypes and haplotypes. Body composition, glucose, insulin, and lipid profile were similar across genotypes and haplotypes in both groups.
CONCLUSIONS: Haplotype TGTG from adiponectin gene variants 45T/G and 276G/T is related to susceptibility to PCOS, and might be associated with increased blood pressure in PCOS.

Zhang Y, Kent JW, Olivier M, et al.
A comprehensive analysis of adiponectin QTLs using SNP association, SNP cis-effects on peripheral blood gene expression and gene expression correlation identified novel metabolic syndrome (MetS) genes with potential role in carcinogenesis and systemic inflammation.
BMC Med Genomics. 2013; 6:14 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Metabolic syndrome (MetS) is an aberration associated with increased risk for cancer and inflammation. Adiponectin, an adipocyte-produced abundant protein hormone, has countering effect on the diabetogenic and atherogenic components of MetS. Plasma levels of adiponectin are negatively correlated with onset of cancer and cancer patient mortality. We previously performed microsatellite linkage analyses using adiponectin as a surrogate marker and revealed two QTLs on chr5 (5p14) and chr14 (14q13).
METHODS: Using individuals from 85 extended families that contributed to the linkage and who were measured for 42 clinical and biologic MetS phenotypes, we tested QTL-based SNP associations, peripheral white blood cell (PWBC) gene expression, and the effects of cis-acting SNPs on gene expression to discover genomic elements that could affect the pathophysiology and complications of MetS.
RESULTS: Adiponectin levels were found to be highly intercorrelated phenotypically with the majority of MetS traits. QTL-specific haplotype-tagging SNPs associated with MetS phenotypes were annotated to 14 genes whose function could influence MetS biology as well as oncogenesis or inflammation. These were mechanistically categorized into four groups: cell-cell adhesion and mobility, signal transduction, transcription and protein sorting. Four genes were highly prioritized: cadherin 18 (CDH18), myosin X (MYO10), anchor protein 6 of AMPK (AKAP6), and neuronal PAS domain protein 3 (NPAS3). PWBC expression was detectable only for the following genes with multi-organ or with multi-function properties: NPAS3, MARCH6, MYO10 and FBXL7. Strong evidence of cis-effects on the expression of MYO10 in PWBC was found with SNPs clustered near the gene's transcription start site. MYO10 expression in PWBC was marginally correlated with body composition (p = 0.065) and adipokine levels in the periphery (p = 0.064). Variants of genes AKAP6, NPAS3, MARCH6 and FBXL7 have been previously reported to be associated with insulin resistance, inflammatory markers or adiposity studies using genome-wide approaches whereas associations of CDH18 and MYO10 with MetS traits have not been reported before.
CONCLUSIONS: Adiponectin QTLs-based SNP association and mRNA expression identified genes that could mediate the association between MetS and cancer or inflammation.

Related: Chromosome 14 Chromosome 5

Kaklamani VG, Hoffmann TJ, Thornton TA, et al.
Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women's Health Initiative.
Breast Cancer Res Treat. 2013; 139(2):461-8 [PubMed] Free Access to Full Article Related Publications
Adiponectin, a protein secreted by the adipose tissue, is an endogenous insulin sensitizer with circulating levels that are decreased in obese and diabetic subjects. Recently, circulating levels of adiponectin have been correlated with breast cancer risk. Our previous work showed that polymorphisms of the adiponectin pathway are associated with breast cancer risk. We conducted the first study of adiponectin pathways in African Americans and Hispanics in the Women's Health Initiative SNP Health Association Resource cohort of 3,642 self-identified Hispanic women and 8,515 self-identified African American women who provided consent for DNA analysis. Single nucleotide polymorphisms (SNPs) from three genes were included in this analysis: ADIPOQ, ADIPOR1, and ADIPOR2. The genome-wide human SNP array 6.0 (909,622 SNPs) ( www.affymetrix.com ) was used. We found that rs1501299, a functional SNP of ADIPOQ that we previously reported was associated with breast cancer risk in a mostly Caucasian population, was also significantly associated with breast cancer incidence (HR for the GG/TG genotype: 1.23; 95 % CI 1.059-1.43) in African American women. We did not find any other SNPs in these genes to be associated with breast cancer incidence. This is the first study assessing the role of adiponectin pathway SNPs in breast cancer risk in African Americans and Hispanics. RS1501299 is significantly associated with breast cancer risk in African American women. As the rates of obesity and diabetes increase in African Americans and Hispanics, adiponectin and its functional SNPs may aid in breast cancer risk assessment.

Related: Breast Cancer Polymorphisms Signal Transduction

Nohara K, Waraich RS, Liu S, et al.
Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.
Am J Physiol Endocrinol Metab. 2013; 304(12):E1321-30 [PubMed] Free Access to Full Article Related Publications
Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

Saxena A, Baliga MS, Ponemone V, et al.
Mucus and adiponectin deficiency: role in chronic inflammation-induced colon cancer.
Int J Colorectal Dis. 2013; 28(9):1267-79 [PubMed] Free Access to Full Article Related Publications
PURPOSE: This study aims to define the role of adiponectin (APN) in preventing goblet cell apoptosis and in differentiation of epithelial cells to goblet cell lineage resulting in greater mucus production and hence greater protection from chronic inflammation-induced colon cancer (CICC).
METHODS: Six- to eight-week-old male APNKO and C57BL/6 (WT) mice were randomly distributed to three treatment groups: DSS, DMH, DSS + DMH and control. Chronic inflammation was induced in DSS and DSS + DMH group by administrating 2 % DSS in drinking water for 5 days followed by 5 days of normal drinking water and this constitutes one DSS cycle. Three cycles of DSS were administered to induce chronic inflammation. Cancer was induced in both APNKO and WT mice in DMH and DSS + DMH groups by intraperitoneal injections of DMH (20 mg/kg body weight) once for DSS + DMH group and once per week for 12 weeks for DMH group. On day 129, the colon tissue was dissected for mucus thickness measurements and for genomic studies. HT29-C1.16E and Ls174T cells were used for several genomic and siRNA studies.
RESULTS: APNKO mice have more tumors and tumor area in DSS + DMH group than WT mice. APN deficiency downregulated goblet to epithelial cell ratio and enhanced the colonic mucosal erosion with reduced mucus thickness. APN increases Muc2 production with no affect on Muc1 production. APN abated goblet cell apoptosis, while APN deficiency reduced epithelial to goblet cell differentiation.
CONCLUSION: APN may be involved in reducing the severity of CICC by preventing goblet cell apoptosis and increasing epithelial to goblet cell differentiation.

Related: Apoptosis TNF

Pau C, Saxena R, Welt CK
Evaluating reported candidate gene associations with polycystic ovary syndrome.
Fertil Steril. 2013; 99(6):1774-8 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To replicate variants in candidate genes associated with polycystic ovary syndrome (PCOS) in a population of European women with PCOS and control subjects.
DESIGN: Case-control association analysis and meta-analysis.
SETTING: Major academic hospital.
PATIENT(S): Women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years.
INTERVENTION(S): Variants previously associated with PCOS in candidate gene studies were genotyped (n = 39). Metabolic, reproductive, and anthropomorphic parameters were examined as a function of the candidate variants. All genetic association analyses were adjusted for age, body mass index, and ancestry and were reported after correction for multiple testing.
MAIN OUTCOME MEASURE(S): Association of candidate gene variants with PCOS.
RESULT(S): Three variants, rs3797179 (SRD5A1), rs12473543 (POMC), and rs1501299 (ADIPOQ), were nominally associated with PCOS. However, they did not remain significant after correction for multiple testing, and none of the variants replicated in a sufficiently powered meta-analysis. Variants in the FBN3 gene (rs17202517 and rs73503752) were associated with smaller waist circumferences, and variant rs727428 in the SHBG gene was associated with lower sex hormone-binding globulin levels.
CONCLUSION(S): Previously identified variants in candidate genes do not seem to be associated with PCOS risk.

Batista ML, Olivan M, Alcantara PS, et al.
Adipose tissue-derived factors as potential biomarkers in cachectic cancer patients.
Cytokine. 2013; 61(2):532-9 [PubMed] Related Publications
Cachexia, a paraneoplastic syndrome markedly associated with worsened prognosis in cancer patients, provokes profound wasting of both lean and adipose mass in an association with a state of metabolic "chaos". The white adipose tissue responds to cachexia with marked local inflammation and may be thus a relevant contributor to systemic inflammation. To address this hypothesis we examined the correlation between tissue expression of adipokines and plasma concentration in cachectic and stable weight patients with or without cancer. Adiponectin and liver-derived CRP concentration were significantly higher in the cachectic groups when compared with stable weight patients (P<0.01). The concentration of plasma IL-6 was higher (11.4-fold) in the cancer cachectic group when compared with weight-stable controls, and presented a significant correlation with the presence of cancer (P<0.001). A marked increase (5-fold) in IL-6 as a result of the interaction between the presence of cachexia and the presence of tumour was observed in the subcutaneous tissue of the patients, yet not in the visceral depot. Plasma adiponectin levels were higher in cachectic cancer patients, compared with stable weight cancer patients individually matched by age, sex, and BMI, and the subcutaneous depot was found to be the main contributing tissue, rather than the visceral pad. Based on the results we concluded that the subcutaneous adipose tissue is associated with plasma changes that may function as markers of cachexia.

Related: IL10 Cancer Prevention and Risk Reduction TNF

Yang Y, Zhang F, Ding R, et al.
ADIPOQ gene polymorphisms and cancer risk: a meta-analysis.
Cytokine. 2013; 61(2):565-71 [PubMed] Related Publications
The results of studies investigating the association between ADIPOQ gene polymorphisms and risk of cancer have been inconsistent and often contradictory. The present meta-analysis was conducted in order to overcome the limitations of any individual study and to provide a more precise overall effect estimate. Relevant studies were identified by searching PubMed and Embase for articles published through May 2012. The strength of the relationship between the ADIPOQ gene and risk of cancer was assessed using odds ratios (ORs). Either a fixed-effects or a random-effects model was used to calculate the overall risk estimates. Fifteen studies were included and five SNPs were considered. A significant association was found between SNP rs2241766 and risk of cancer in the recessive genetic model (OR: 0.768, 95% CI: [0.626,0.942], P=0.011); a significant relationship was also found between SNP rs1501299 and risk of cancer in both an allele contrast (OR: 0.141, 95%CI: [0.113,0.176], P<0.001) and the dominant genetic model (OR: 0.904, 95%CI: [0.830,0.985], P=0.021); no association was found with the rs266729, rs822395, or rs822396 SNPs. Adjusted ORs were also considered, but no statistically significant association was found in homozygote contrasts for any of the five SNPs after adjustment. Our results suggest that two polymorphisms, SNP rs2241766 and SNP rs1501299, of the ADIPOQ gene may be associated with reduced risk of cancer. However, the overall strength of association is mild to moderate, and additional well-designed studies are needed to confirm the present conclusion.

Related: Cancer Prevention and Risk Reduction

Rahal OM, Pabona JM, Kelly T, et al.
Suppression of Wnt1-induced mammary tumor growth and lower serum insulin in offspring exposed to maternal blueberry diet suggest early dietary influence on developmental programming.
Carcinogenesis. 2013; 34(2):464-74 [PubMed] Free Access to Full Article Related Publications
Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. In this study, we investigated whether early exposure to blueberry (BB) via maternal diet alters oncogene Wnt1-induced mammary tumorigenesis in offspring. Wnt1-transgenic female mice were exposed to maternal Casein (CAS, control) or blueberry-supplemented (CAS + 3%BB) diets throughout pregnancy and lactation. Offspring were weaned to CAS and mammary tumor development was followed until age 8 months. Tumor incidence and latency were similar for both groups; however, tumor weight at killing and tumor volume within 2 weeks of initial detection were lower (by 50 and 60%, respectively) in offspring of BB- versus control-fed dams. Dietary BB exposure beginning at weaning did not alter mammary tumor parameters. Tumors from maternal BB-exposed offspring showed higher tumor suppressor (Pten and Cdh1) and lower proproliferative (Ccnd1), anti-apoptotic (Bcl2) and proangiogenic (Figf, Flt1 and Ephb4) transcript levels, and displayed attenuated microvessel density. Expression of Pten and Cdh1 genes was also higher in mammary tissues of maternal BB-exposed offspring. Mammary tissues and tumors of maternal BB-exposed offspring showed increased chromatin-modifying enzyme Dnmt1 and Ezh2 transcript levels. Body weight, serum insulin and serum leptin/adiponectin ratio were lower for maternal BB-exposed than control tumor-bearing offspring. Tumor weights and serum insulin were positively correlated. Results suggest that dietary influences on the maternal environment contribute to key developmental programs in the mammary gland to modify breast cancer outcome in adult progeny.

Related: Signal Transduction

Xu Y, He B, Pan Y, et al.
The roles of ADIPOQ genetic variations in cancer risk: evidence from published studies.
Mol Biol Rep. 2013; 40(2):1135-44 [PubMed] Related Publications
Adiponectin produced by adipose tissue, which is involved in complex diseases related to obesity, such as cancer. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. However, epidemiological results were inconsistent. To examine this controversy, we assessed reported studies of association between ADIPOQ polymorphisms and cancer risk. Relevant studies were selected by PUBMED, EMBASE update to January 12th, 2012. According to the acceptance and exclusion criteria, 15 studies involved three polymorphisms (rs266729, rs2241766, rs1501299) of ADIPOQ were included. Summary odds ratio (ORs) and 95 % confidence intervals (CIs) were calculated using random-effect or fixed-effect models based on the heterogeneity of included studies. A total of 15 case-control studies related rs266729 (5,615 cases and 6,425 controls), rs2241766 (5,318 cases and 6,118 controls) and rs1501299 (3,751 cases and 5,104 controls) were included to analyze the ADIPOQ polymorphisms and cancer risk. For rs1501299, T allele was associated with decreased cancer risk. In addition, cancer type subgroup analysis revealed T allele was associated with decreased colorectal and prostate cancer risk. Ethnicity subgroup analysis observed a decreased risk in both Asian and Caucasian descendents. As to rs2241766, a borderline decreased cancer risk was observed. This meta-analysis indicated T allele of rs1501299 was an obvious protection factor for cancer risk, and G allele of rs2241766 was a potential protection factor for cancer risk, especially in Caucasian descendents. Further studies should be performed to clarify the roles of ADIPOQ polymorphisms in the cancer risk.

Related: Cancer Prevention and Risk Reduction Polymorphisms


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