{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:26:54Z","timestamp":1790864814304,"version":"4.1.0"},"reference-count":143,"publisher":"Bioscientifica","issue":"6","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,27]]},"abstract":"<jats:p>Meta-analyses from 2018\u20132022 have shown that obesity increases the risk of various cancers such as acute myeloid lymphoma, chronic myeloid lymphoma, diffuse beta cell lymphoma, Hodgkin's lymphoma, leukemia, multiple myeloma, non-Hodgkin's lymphoma, bladder, breast, cholangiocarcinoma, colorectal, ovarian, esophageal, kidney, liver, prostate, thyroid, and uterus. Contextually, obesity, and its comorbidities, is the largest, most lethal pandemics in the history of mankind; hence, identification of underlying mechanisms is needed to adequately address this global health threat. Herein, we present the metabolic and hormonal mechanisms linked to obesity that might etiologically contribute to neoplasia, including hyperinsulinemia and putative places in the insulin-signaling pathway. Excess insulin, acting as a growth factor, might contribute to tumorigenesis, while abundant ATP and GDP supply the additional energy needed for proliferation of rapidly dividing cells. Our observations in the Ecuadorian cohort of subjects with Laron syndrome (ELS) prove that obesity does not always associate with increased cancer risk. Indeed, despite excess body fat from birth to death, these individuals display a diminished incidence of cancer when compared to their age- and sex-matched relatives. Furthermore, in cell cultures exposed to potent oxidizing agents, addition of ELS serum induces less DNA damage as well as increased apoptosis. ELS individuals have absent growth hormone (GH) counter-regulatory effects in carbohydrate metabolism due to a defective GH receptor. The corresponding biochemical phenotype includes extremely low basal serum concentrations of insulin and insulin-like growth factor-I, lower basal glucose and triglyceride (TG) levels, and diminished glucose, TG, and insulin responses to orally administered glucose or to a mixed meal.<\/jats:p>","DOI":"10.1530\/erc-22-0389","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T07:11:47Z","timestamp":1679987507000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":9,"title":["Cancer in Ecuadorian subjects with Laron syndrome (ELS)"],"prefix":"10.1530","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9298-6484","authenticated-orcid":true,"given":"Jaime","family":"Guevara-Aguirre","sequence":"first","affiliation":[{"name":"Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s\/n y Pampite, Cumbay\u00e1, Quito, Ecuador"},{"name":"Instituto de Endocrinolog\u00eda IEMYR, Quito, Ecuador"},{"name":"Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s\/n y Pampite, Cumbay\u00e1, Quito, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Pazmi\u00f1o","sequence":"additional","affiliation":[{"name":"Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s\/n y Pampite, Cumbay\u00e1, Quito, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Acosta","sequence":"additional","affiliation":[{"name":"Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s\/n y Pampite, Cumbay\u00e1, Quito, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannette","family":"Saavedra","sequence":"additional","affiliation":[{"name":"Instituto de Endocrinolog\u00eda IEMYR, Quito, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Lescano","sequence":"additional","affiliation":[{"name":"Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s\/n y Pampite, Cumbay\u00e1, Quito, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Guevara","sequence":"additional","affiliation":[{"name":"Instituto de Endocrinolog\u00eda IEMYR, Quito, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio W D","family":"Gavilanes","sequence":"additional","affiliation":[{"name":"Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Annals of Oncology","first-page":"528","article-title":"Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies","volume":"30","author":"Abar","year":"2019","unstructured":"Abar LSobiecki JGCariolou MNanu NVieira ARStevens CAune DGreenwood DCChan DSM & Norat T2019Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies. Annals of Oncology30528\u2013541. (https:\/\/doi.org\/10.1093\/annonc\/mdz045)"},{"key":"bib2","series-title":"Cancer Biomarkers: Section A of Disease Markers","first-page":"653","article-title":"Quantification of insulin receptor mRNA splice variants as a diagnostic tumor marker in breast cancer","volume":"15","author":"Aljada","year":"2015","unstructured":"Aljada ASaleh AMAl-Aqeel SMShamsa HBAl-Bawab AAl Dubayee M & Ahmed AA2015Quantification of insulin receptor mRNA splice variants as a diagnostic tumor marker in breast cancer. Cancer Biomarkers: Section A of Disease Markers15653\u2013661. (https:\/\/doi.org\/10.3233\/CBM-150505)"},{"key":"bib3","series-title":"Experimental Diabetes Research","article-title":"Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms","volume":"2012","author":"Arcidiacono","year":"2012","unstructured":"Arcidiacono BIiritano SNocera APossidente KNevolo MTVentura VFoti DChiefari E & Brunetti A2012Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Experimental Diabetes Research2012 789174. (https:\/\/doi.org\/10.1155\/2012\/789174)"},{"key":"bib4","series-title":"International Journal of Molecular Sciences","article-title":"Hyperinsulinemia promotes esophageal cancer development in a surgically-induced duodeno-esophageal reflux murine model","volume":"19","author":"Arcidiacono","year":"2018","unstructured":"Arcidiacono DDedja AGiacometti CFassan MNucci DFrancia SFabris FZaramella AGallagher EJCassaro M, 2018Hyperinsulinemia promotes esophageal cancer development in a surgically-induced duodeno-esophageal reflux murine model. International Journal of Molecular Sciences191198. (https:\/\/doi.org\/10.3390\/ijms19041198)"},{"key":"bib5","series-title":"American Naturalist","first-page":"116","article-title":"The role of factor mutations in evolution","volume":"52","author":"Babcock","year":"1918","unstructured":"Babcock EB1918The role of factor mutations in evolution. American Naturalist52116\u2013128. (https:\/\/doi.org\/10.1086\/279659)"},{"key":"bib6","series-title":"Endocrine Reviews","first-page":"586","article-title":"Insulin receptor isoforms and insulin receptor\/insulin-like growth factor receptor hybrids in physiology and disease","volume":"30","author":"Belfiore","year":"2009","unstructured":"Belfiore AFrasca FPandini GSciacca L & Vigneri R2009Insulin receptor isoforms and insulin receptor\/insulin-like growth factor receptor hybrids in physiology and disease. Endocrine Reviews30586\u2013623. (https:\/\/doi.org\/10.1210\/er.2008-0047)"},{"key":"bib7","series-title":"Endocrine Reviews","first-page":"379","article-title":"Insulin receptor isoforms in physiology and disease: an updated view","volume":"38","author":"Belfiore","year":"2017","unstructured":"Belfiore AMalaguarnera RVella VLawrence MCSciacca LFrasca FMorrione A & Vigneri R2017Insulin receptor isoforms in physiology and disease: an updated view. Endocrine Reviews38379\u2013431. (https:\/\/doi.org\/10.1210\/er.2017-00073)"},{"key":"bib8","series-title":"Human Mutation","first-page":"24","article-title":"Mutation creating a new splice site in the growth hormone receptor genes of 37 Ecuadorean patients with Laron syndrome","volume":"1","author":"Berg","year":"1992","unstructured":"Berg MAGuevara-Aguirre JRosenbloom ALRosenfeld RG & Francke U1992Mutation creating a new splice site in the growth hormone receptor genes of 37 Ecuadorean patients with Laron syndrome. Human Mutation124\u201332. (https:\/\/doi.org\/10.1002\/humu.1380010105)"},{"key":"bib9","series-title":"Nature","first-page":"108","article-title":"Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides","volume":"508","author":"Birsoy","year":"2014","unstructured":"Birsoy KPossemato RLorbeer FKBayraktar ECThiru PYucel BWang TChen WWClish CB & Sabatini DM2014Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. Nature508108\u2013112. (https:\/\/doi.org\/10.1038\/nature13110)"},{"key":"bib10","series-title":"European Journal of Endocrinology","first-page":"R147","article-title":"Management of endocrine disease: acromegaly and cancer: an old debate revisited","volume":"175","author":"Boguszewski","year":"2016","unstructured":"Boguszewski CL & Ayuk J2016Management of endocrine disease: acromegaly and cancer: an old debate revisited. European Journal of Endocrinology175R147\u2013R156. (https:\/\/doi.org\/10.1530\/EJE-16-0178)"},{"key":"bib11","series-title":"BMC Cancer","article-title":"A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates","volume":"10","author":"Calabrese","year":"2010","unstructured":"Calabrese P & Shibata D2010A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates. BMC Cancer10 3. (https:\/\/doi.org\/10.1186\/1471-2407-10-3)"},{"key":"bib12","series-title":"Cancer Epidemiology","first-page":"31","article-title":"Obesity and renal cell carcinoma risk by histologic subtype: a nested case-control study and meta-analysis","volume":"56","author":"Callahan","year":"2018","unstructured":"Callahan CLHofmann JNCorley DAZhao WKShuch BChow WH & Purdue MP2018Obesity and renal cell carcinoma risk by histologic subtype: a nested case-control study and meta-analysis. Cancer Epidemiology5631\u201337. (https:\/\/doi.org\/10.1016\/j.canep.2018.07.002)"},{"key":"bib13","series-title":"Frontiers in Endocrinology (Lausanne)","article-title":"Beta cell dysfunction and insulin resistance","volume":"4","author":"Cerf","year":"2013","unstructured":"Cerf ME2013Beta cell dysfunction and insulin resistance. Frontiers in Endocrinology (Lausanne)4 37. (https:\/\/doi.org\/10.3389\/fendo.2013.00037)"},{"key":"bib14","series-title":"PLoS One","article-title":"Inferring causal pathways among three or more variables from steady-state correlations in a homeostatic system","volume":"13","author":"Chawla","year":"2018","unstructured":"Chawla SPund AB VKulkarni SDiwekar-Joshi M & Watve M2018Inferring causal pathways among three or more variables from steady-state correlations in a homeostatic system. PLoS One13 e0204755. (https:\/\/doi.org\/10.1371\/journal.pone.0204755)"},{"key":"bib15","series-title":"Cancer Research","first-page":"3974","article-title":"Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors","volume":"73","author":"Chettouh","year":"2013","unstructured":"Chettouh HFartoux LAoudjehane LWendum DClap\u00e9ron AChr\u00e9tien YRey CScatton OSoubrane OConti F, 2013Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors. Cancer Research733974\u20133986. (https:\/\/doi.org\/10.1158\/0008-5472.CAN-12-3824)"},{"key":"bib16","series-title":"International Journal of Molecular Sciences","article-title":"Insulin resistance and cancer: in search for a causal link","volume":"22","author":"Chiefari","year":"2021","unstructured":"Chiefari EMirabelli MLa Vignera STanyola\u00e7 SFoti DPAversa A & Brunetti A2021Insulin resistance and cancer: in search for a causal link. International Journal of Molecular Sciences2211137. (https:\/\/doi.org\/10.3390\/ijms222011137)"},{"key":"bib17","series-title":"Molecular Cell","first-page":"474","article-title":"Glucose-induced \u03b2-catenin acetylation enhances Wnt signaling in cancer","volume":"49","author":"Chocarro-Calvo","year":"2013","unstructured":"Chocarro-Calvo AGarc\u00eda-Mart\u00ednez JMArdila-Gonz\u00e1lez SDe la Vieja A & Garc\u00eda-Jim\u00e9nez C2013Glucose-induced \u03b2-catenin acetylation enhances Wnt signaling in cancer. Molecular Cell49474\u2013486. (https:\/\/doi.org\/10.1016\/j.molcel.2012.11.022)"},{"key":"bib18","series-title":"Annual Review of Nutrition","first-page":"393","article-title":"Nutritional regulation of IGF-I and IGF binding proteins","volume":"11","author":"Clemmons","year":"1991","unstructured":"Clemmons DR & Underwood LE1991Nutritional regulation of IGF-I and IGF binding proteins. Annual Review of Nutrition11393\u2013412. (https:\/\/doi.org\/10.1146\/annurev.nu.11.070191.002141)"},{"key":"bib19","series-title":"Endocrine Reviews","first-page":"102","article-title":"Systemic complications of acromegaly: epidemiology, pathogenesis, and management","volume":"25","author":"Colao","year":"2004","unstructured":"Colao AFerone DMarzullo P & Lombardi G2004Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocrine Reviews25102\u2013152. (https:\/\/doi.org\/10.1210\/er.2002-0022)"},{"key":"bib20","series-title":"Physiology","author":"Constanzo","year":"2018","unstructured":"Constanzo L2018Physiology6th ed.Barcelona, Espa\u00f1a: Elsevier."},{"key":"bib21","series-title":"Diabetes","first-page":"4","article-title":"Banting lecture 2011: hyperinsulinemia: cause or consequence?","volume":"61","author":"Corkey","year":"2012","unstructured":"Corkey BE2012Banting lecture 2011: hyperinsulinemia: cause or consequence?Diabetes614\u201313. (https:\/\/doi.org\/10.2337\/db11-1483)"},{"key":"bib22","series-title":"Comprehensive Physiology","first-page":"237","article-title":"Contribution of adipose tissue to development of cancer","volume":"8","author":"Cozzo","year":"2017","unstructured":"Cozzo AJFuller AM & Makowski L2017Contribution of adipose tissue to development of cancer. Comprehensive Physiology8237\u2013282. (https:\/\/doi.org\/10.1002\/cphy.c170008)"},{"key":"bib23","series-title":"Medicine (Baltimore)","article-title":"A meta-analysis of the influence of body mass index on the clinicopathologic progression of papillary thyroid carcinoma","volume":"100","author":"Cui","year":"2021","unstructured":"Cui NSun Q & Chen L2021A meta-analysis of the influence of body mass index on the clinicopathologic progression of papillary thyroid carcinoma. Medicine (Baltimore)100 e26882. (https:\/\/doi.org\/10.1097\/MD.0000000000026882)"},{"key":"bib24","year":"2000","unstructured":"De Meyts P2000 The insulin receptor and its signal transduction network. In Endotext. EdsDe GrootLJ, et al. South Dartmouth, MA, USA: MDText.com, Inc. (available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK378978\/)"},{"key":"bib25","series-title":"Diabetology and Metabolic Syndrome","article-title":"Mechanism of the mitogenic influence of hyperinsulinemia","volume":"3","author":"Draznin","year":"2011","unstructured":"Draznin B2011Mechanism of the mitogenic influence of hyperinsulinemia. Diabetology and Metabolic Syndrome3 10. (https:\/\/doi.org\/10.1186\/1758-5996-3-10)"},{"key":"bib26","series-title":"Acta Diabetologica","first-page":"945","article-title":"Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma","volume":"53","author":"Dugnani","year":"2016","unstructured":"Dugnani EBalzano GPasquale VScavini MAleotti FLiberati DDi Terlizzi GGandolfi APetrella GReni M, 2016Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma. Acta Diabetologica53945\u2013956. (https:\/\/doi.org\/10.1007\/s00592-016-0893-6)"},{"key":"bib27","series-title":"PNAS","first-page":"8014","article-title":"Expression of a functional human insulin receptor from a cloned cDNA in Chinese hamster ovary cells","volume":"82","author":"Ebina","year":"1985","unstructured":"Ebina YEdery MEllis LStandring DBeaudoin JRoth RA & Rutter WJ1985Expression of a functional human insulin receptor from a cloned cDNA in Chinese hamster ovary cells. PNAS828014\u20138018. (https:\/\/doi.org\/10.1073\/pnas.82.23.8014)"},{"key":"bib28","series-title":"Journal of Diabetes Research","article-title":"The role of insulin receptor isoforms in diabetes and its metabolic and vascular complications","volume":"2017","author":"Escribano","year":"2017","unstructured":"Escribano OBeneit NRubio-Long\u00e1s CL\u00f3pez-Pastor AR & G\u00f3mez-Hern\u00e1ndez A2017The role of insulin receptor isoforms in diabetes and its metabolic and vascular complications. Journal of Diabetes Research2017 1403206. (https:\/\/doi.org\/10.1155\/2017\/1403206)"},{"key":"bib29","series-title":"Breast Cancer Research","article-title":"Hyperinsulinemia enhances c-Myc-mediated mammary tumor development and advances metastatic progression to the lung in a mouse model of type 2 diabetes","volume":"14","author":"Ferguson","year":"2012","unstructured":"Ferguson RDNovosyadlyy RFierz YAlikhani NSun HYakar S & Leroith D2012Hyperinsulinemia enhances c-Myc-mediated mammary tumor development and advances metastatic progression to the lung in a mouse model of type 2 diabetes. Breast Cancer Research14 R8. (https:\/\/doi.org\/10.1186\/bcr3089)"},{"key":"bib30","series-title":"Oncogene","first-page":"3213","article-title":"Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia","volume":"31","author":"Gallagher","year":"2012","unstructured":"Gallagher EJFierz YVijayakumar AHaddad NYakar S & LeRoith D2012Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. Oncogene313213\u20133222. (https:\/\/doi.org\/10.1038\/onc.2011.495)"},{"key":"bib31","series-title":"Physiological Reviews","first-page":"727","article-title":"Obesity and diabetes: the increased risk of cancer and cancer-related mortality","volume":"95","author":"Gallagher","year":"2015","unstructured":"Gallagher EJ & LeRoith D2015Obesity and diabetes: the increased risk of cancer and cancer-related mortality. Physiological Reviews95727\u2013748. (https:\/\/doi.org\/10.1152\/physrev.00030.2014)"},{"key":"bib32","series-title":"Nutrition and Cancer","first-page":"908","article-title":"The comparison of different obesity indexes and the risk of lung cancer: a meta-analysis of prospective cohort studies","volume":"71","author":"Gao","year":"2019","unstructured":"Gao JLin XHe YFu YWu YLiao JWu Y & Lian X2019The comparison of different obesity indexes and the risk of lung cancer: a meta-analysis of prospective cohort studies. Nutrition and Cancer71908\u2013921. (https:\/\/doi.org\/10.1080\/01635581.2019.1595037)"},{"key":"bib33","series-title":"Journal of Molecular Endocrinology","first-page":"R51","article-title":"A new link between diabetes and cancer: enhanced WNT\/\u03b2-catenin signaling by high glucose","volume":"52","author":"Garc\u00eda-Jim\u00e9nez","year":"2014","unstructured":"Garc\u00eda-Jim\u00e9nez CGarc\u00eda-Mart\u00ednez JMChocarro-Calvo A & De la Vieja A2014A new link between diabetes and cancer: enhanced WNT\/\u03b2-catenin signaling by high glucose. Journal of Molecular Endocrinology52R51\u2013R66. (https:\/\/doi.org\/10.1530\/JME-13-0152)"},{"key":"bib34","series-title":"Diabetes, Obesity and Metabolism","first-page":"97","article-title":"Diabetes and cancer: two diseases with obesity as a common risk factor","volume":"16","author":"Garg","year":"2014","unstructured":"Garg SKMaurer HReed K & Selagamsetty R2014Diabetes and cancer: two diseases with obesity as a common risk factor. Diabetes, Obesity and Metabolism1697\u2013110. (https:\/\/doi.org\/10.1111\/dom.12124)"},{"key":"bib35","series-title":"Molecular Biology of the Cell","first-page":"4484","article-title":"Insulin signaling diverges into Akt-dependent and -independent signals to regulate the recruitment\/docking and the fusion of GLUT4 vesicles to the plasma membrane","volume":"17","author":"Gonzalez","year":"2006","unstructured":"Gonzalez E & McGraw TE2006Insulin signaling diverges into Akt-dependent and -independent signals to regulate the recruitment\/docking and the fusion of GLUT4 vesicles to the plasma membrane. Molecular Biology of the Cell174484\u20134493. (https:\/\/doi.org\/10.1091\/mbc.e06-07-0585)"},{"key":"bib36","series-title":"Breast Cancer Research and Treatment","first-page":"517","article-title":"High insulin levels in newly diagnosed breast cancer patients reflect underlying insulin resistance and are associated with components of the insulin resistance syndrome","volume":"114","author":"Goodwin","year":"2009","unstructured":"Goodwin PJEnnis MBahl MFantus IGPritchard KITrudeau MEKoo J & Hood N2009High insulin levels in newly diagnosed breast cancer patients reflect underlying insulin resistance and are associated with components of the insulin resistance syndrome. Breast Cancer Research and Treatment114517\u2013525. (https:\/\/doi.org\/10.1007\/s10549-008-0019-0)"},{"key":"bib37","series-title":"Journal of Clinical Oncology","first-page":"164","article-title":"Insulin- and obesity-related variables in early-stage breast cancer: correlations and time course of prognostic associations","volume":"30","author":"Goodwin","year":"2012","unstructured":"Goodwin PJEnnis MPritchard KITrudeau MEKoo JTaylor SK & Hood N2012Insulin- and obesity-related variables in early-stage breast cancer: correlations and time course of prognostic associations. Journal of Clinical Oncology30164\u2013171. (https:\/\/doi.org\/10.1200\/JCO.2011.36.2723)"},{"key":"bib38","series-title":"Annual Review of Medicine","first-page":"281","article-title":"Impact of the obesity epidemic on cancer","volume":"66","author":"Goodwin","year":"2015","unstructured":"Goodwin PJ & Stambolic V2015Impact of the obesity epidemic on cancer. Annual Review of Medicine66281\u2013296. (https:\/\/doi.org\/10.1146\/annurev-med-051613-012328)"},{"key":"bib39","series-title":"Science Translational Medicine","article-title":"Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans","volume":"3","author":"Guevara-Aguirre","year":"2011","unstructured":"Guevara-Aguirre JBalasubramanian PGuevara-Aguirre MWei MMadia FCheng CWHwang DMartin-Montalvo ASaavedra JIngles S, 2011Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Science Translational Medicine3 70ra13. (https:\/\/doi.org\/10.1126\/scitranslmed.3001845)"},{"key":"bib40","series-title":"Reviews in Endocrine and Metabolic Disorders","first-page":"59","article-title":"Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador","volume":"22","author":"Guevara-Aguirre","year":"2021a","unstructured":"Guevara-Aguirre JBautista CTorres CPe\u00f1a GGuevara CPalacios CGuevara A & Gavilanes AWD2021aInsights from the clinical phenotype of subjects with Laron syndrome in Ecuador. Reviews in Endocrine and Metabolic Disorders2259\u201370. (https:\/\/doi.org\/10.1007\/s11154-020-09602-4)"},{"key":"bib41","series-title":"Diabetologia","first-page":"37","article-title":"Obesity, diabetes and cancer: insight into the relationship from a cohort with growth hormone receptor deficiency","volume":"58","author":"Guevara-Aguirre","year":"2015","unstructured":"Guevara-Aguirre J & Rosenbloom AL2015Obesity, diabetes and cancer: insight into the relationship from a cohort with growth hormone receptor deficiency. Diabetologia5837\u201342. (https:\/\/doi.org\/10.1007\/s00125-014-3397-3)"},{"key":"bib42","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"2589","article-title":"GH receptor deficiency in Ecuadorian adults is associated with obesity and enhanced insulin sensitivity","volume":"100","author":"Guevara-Aguirre","year":"2015","unstructured":"Guevara-Aguirre JRosenbloom ALBalasubramanian PTeran EGuevara-Aguirre MGuevara CProcel PAlfaras IDe Cabo RDi Biase S, 2015GH receptor deficiency in Ecuadorian adults is associated with obesity and enhanced insulin sensitivity. Journal of Clinical Endocrinology and Metabolism1002589\u20132596. (https:\/\/doi.org\/10.1210\/jc.2015-1678)"},{"key":"bib43","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"417","article-title":"Growth hormone receptor deficiency in Ecuador: clinical and biochemical phenotype in two populations","volume":"76","author":"Guevara-Aguirre","year":"1993","unstructured":"Guevara-Aguirre JRosenbloom ALFielder PJDiamond FB & Rosenfeld RG1993Growth hormone receptor deficiency in Ecuador: clinical and biochemical phenotype in two populations. Journal of Clinical Endocrinology and Metabolism76417\u2013423. (https:\/\/doi.org\/10.1210\/jcem.76.2.7679400)"},{"key":"bib44","series-title":"Molecular and Cellular Endocrinology","article-title":"IGF-I deficiency and enhanced insulin sensitivity due to a mutated growth hormone receptor gene in humans","volume":"519","author":"Guevara-Aguirre","year":"2021b","unstructured":"Guevara-Aguirre JTorres CPe\u00f1a GPalacios MBautista CGuevara A & Gavilanes AW2021bIGF-I deficiency and enhanced insulin sensitivity due to a mutated growth hormone receptor gene in humans. Molecular and Cellular Endocrinology519 111044. (https:\/\/doi.org\/10.1016\/j.mce.2020.111044)"},{"key":"bib45","series-title":"Acta Pharmaceutica Sinica B","first-page":"358","article-title":"Glycolysis in the control of blood glucose homeostasis","volume":"2","author":"Guo","year":"2012","unstructured":"Guo XLi HXu HWoo SDong HLu FLange AJ & Wu C2012Glycolysis in the control of blood glucose homeostasis. Acta Pharmaceutica Sinica B2358\u2013367. (https:\/\/doi.org\/10.1016\/j.apsb.2012.06.002)"},{"key":"bib46","series-title":"Nature Reviews. Molecular Cell Biology","first-page":"31","article-title":"Biochemical and cellular properties of insulin receptor signalling","volume":"19","author":"Haeusler","year":"2018","unstructured":"Haeusler RAMcGraw TE & Accili D2018Biochemical and cellular properties of insulin receptor signalling. Nature Reviews. Molecular Cell Biology1931\u201344. (https:\/\/doi.org\/10.1038\/nrm.2017.89)"},{"key":"bib47","series-title":"Cell","first-page":"646","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","unstructured":"Hanahan D & Weinberg RA2011Hallmarks of cancer: the next generation. Cell144646\u2013674. (https:\/\/doi.org\/10.1016\/j.cell.2011.02.013)"},{"key":"bib48","series-title":"Growth Hormone and IGF Research","first-page":"108","article-title":"Quantifying insulin receptor isoform expression in FFPE breast tumors","volume":"22","author":"Harrington","year":"2012","unstructured":"Harrington SCWeroha SJReynolds CSuman VJLingle WL & Haluska P2012Quantifying insulin receptor isoform expression in FFPE breast tumors. Growth Hormone and IGF Research22108\u2013115. (https:\/\/doi.org\/10.1016\/j.ghir.2012.04.001)"},{"key":"bib49","series-title":"Cancer Causes and Control","first-page":"431","article-title":"Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen","volume":"31","author":"Harrison","year":"2020","unstructured":"Harrison STilling KTurner ELMartin RMLennon RLane JADonovan JLHamdy FCNeal DEBosch JLHR, 2020Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen. Cancer Causes and Control31431\u2013449. (https:\/\/doi.org\/10.1007\/s10552-020-01291-3)"},{"key":"bib50","series-title":"Maturitas","first-page":"29","article-title":"27-hydroxycholesterol, an endogenous selective estrogen receptor modulator","volume":"104","author":"He","year":"2017","unstructured":"He S & Nelson ER201727-hydroxycholesterol, an endogenous selective estrogen receptor modulator. Maturitas10429\u201335. (https:\/\/doi.org\/10.1016\/j.maturitas.2017.07.014)"},{"key":"bib51","series-title":"Cold Spring Harbor Perspectives in Biology","article-title":"Mutation--the engine of evolution: studying mutation and its role in the evolution of bacteria","volume":"7","author":"Hershberg","year":"2015","unstructured":"Hershberg R2015Mutation--the engine of evolution: studying mutation and its role in the evolution of bacteria. Cold Spring Harbor Perspectives in Biology7 a018077. (https:\/\/doi.org\/10.1101\/cshperspect.a018077)"},{"key":"bib52","series-title":"Carcinogenesis","first-page":"370","article-title":"NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K\/Akt\/mTOR signaling pathway","volume":"40","author":"Huang","year":"2019","unstructured":"Huang YKKang WMMa ZQLiu YQZhou L & Yu JC2019NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K\/Akt\/mTOR signaling pathway. Carcinogenesis40370\u2013379. (https:\/\/doi.org\/10.1093\/carcin\/bgy142)"},{"key":"bib53","series-title":"International Journal of Molecular Sciences","article-title":"Hyperinsulinemia and its pivotal role in aging, obesity, type 2 diabetes, cardiovascular disease and cancer","volume":"22","author":"Janssen","year":"2021","unstructured":"Janssen JAMJL2021Hyperinsulinemia and its pivotal role in aging, obesity, type 2 diabetes, cardiovascular disease and cancer. International Journal of Molecular Sciences227797. (https:\/\/doi.org\/10.3390\/ijms22157797)"},{"key":"bib54","series-title":"JAMA","first-page":"194","article-title":"Fasting serum glucose level and cancer risk in Korean men and women","volume":"293","author":"Jee","year":"2005","unstructured":"Jee SHOhrr HSull JWYun JEJi M & Samet JM2005Fasting serum glucose level and cancer risk in Korean men and women. JAMA293194\u2013202. (https:\/\/doi.org\/10.1001\/jama.293.2.194)"},{"key":"bib55","series-title":"Lung Cancer","first-page":"58","article-title":"The relationship between body-mass index and overall survival in non-small cell lung cancer by sex, smoking status, and race: a pooled analysis of 20,937 International lung Cancer consortium (ILCCO) patients","volume":"152","author":"Jiang","year":"2021","unstructured":"Jiang MFares AFShepshelovich DYang PChristiani DZhang JShiraishi KRyan BMChen CSchwartz AG, 2021The relationship between body-mass index and overall survival in non-small cell lung cancer by sex, smoking status, and race: a pooled analysis of 20,937 International lung Cancer consortium (ILCCO) patients. Lung Cancer15258\u201365. (https:\/\/doi.org\/10.1016\/j.lungcan.2020.11.029)"},{"key":"bib56","series-title":"Proceedings of the Nutrition Society","first-page":"91","article-title":"Energy balance and cancer: the role of insulin and insulin-like growth factor-I","volume":"60","author":"Kaaks","year":"2001","unstructured":"Kaaks R & Lukanova A2001Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proceedings of the Nutrition Society6091\u2013106. (https:\/\/doi.org\/10.1079\/pns200070)"},{"key":"bib57","series-title":"Journal of the National Cancer Institute","first-page":"1592","article-title":"Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women","volume":"92","author":"Kaaks","year":"2000","unstructured":"Kaaks RToniolo PAkhmedkhanov ALukanova ABiessy CDechaud HRinaldi SZeleniuch-Jacquotte AShore RE & Riboli E2000Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. Journal of the National Cancer Institute921592\u20131600. (https:\/\/doi.org\/10.1093\/jnci\/92.19.1592)"},{"key":"bib58","series-title":"Journal of Clinical Investigation","first-page":"3990","article-title":"Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome","volume":"129","author":"Kahn","year":"2019","unstructured":"Kahn CRWang G & Lee KY2019Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. Journal of Clinical Investigation1293990\u20134000. (https:\/\/doi.org\/10.1172\/JCI129187)"},{"key":"bib59","series-title":"eLife","article-title":"Akt phosphorylates insulin receptor substrate to limit PI3K-mediated PIP3 synthesis","volume":"10","author":"Kearney","year":"2021","unstructured":"Kearney ALNorris DMGhomlaghi MKin Lok Wong MHumphrey SJCarroll LYang GCooke KCYang PGeddes TA, Akt phosphorylates insulin receptor substrate to limit PI3K-mediated PIP3 synthesis. eLife202110. (https:\/\/doi.org\/10.7554\/eLife.66942)"},{"key":"bib60","series-title":"Molecular and Cellular Biology","first-page":"5800","article-title":"Akt\/protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria","volume":"19","author":"Kennedy","year":"1999","unstructured":"Kennedy SGKandel ESCross TK & Hay N1999Akt\/protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Molecular and Cellular Biology195800\u20135810. (https:\/\/doi.org\/10.1128\/MCB.19.8.5800)"},{"key":"bib61","series-title":"Diabetes and Metabolism Journal","first-page":"799","article-title":"Obesity, diabetes, and increased cancer progression","volume":"45","author":"Kim","year":"2021","unstructured":"Kim DS & Scherer PE2021Obesity, diabetes, and increased cancer progression. Diabetes and Metabolism Journal45799\u2013812. (https:\/\/doi.org\/10.4093\/dmj.2021.0077)"},{"key":"bib62","series-title":"Nature Reviews. Cancer","first-page":"325","article-title":"Otto Warburg\u2019s contributions to current concepts of cancer metabolism","volume":"11","author":"Koppenol","year":"2011","unstructured":"Koppenol WHBounds PL & Dang CV2011Otto Warburg\u2019s contributions to current concepts of cancer metabolism. Nature Reviews. Cancer11325\u2013337. (https:\/\/doi.org\/10.1038\/nrc3038)"},{"key":"bib63","series-title":"Metabolism: Clinical and Experimental","article-title":"Body fatness associations with cancer: evidence from recent epidemiological studies and future directions","volume":"137","author":"Larsson","year":"2022","unstructured":"Larsson SCSpyrou N & Mantzoros CS2022Body fatness associations with cancer: evidence from recent epidemiological studies and future directions. Metabolism: Clinical and Experimental137 155326. (https:\/\/doi.org\/10.1016\/j.metabol.2022.155326)"},{"key":"bib64","series-title":"Nutrients","article-title":"A meta-analysis of obesity and risk of colorectal cancer in patients with Lynch syndrome: the impact of sex and genetics","volume":"13","author":"Lazzeroni","year":"2021","unstructured":"Lazzeroni MBellerba FCalvello MMacrae FWin AKJenkins MSerrano DMarabelli MCagnacci STolva G, 2021A meta-analysis of obesity and risk of colorectal cancer in patients with Lynch syndrome: the impact of sex and genetics. Nutrients13. (https:\/\/doi.org\/10.3390\/nu13051736)"},{"key":"bib65","series-title":"Nutrition and Cancer","first-page":"1601","article-title":"Excessive body fat at a young age increases the risk of colorectal cancer: a systematic review and meta-analysis","volume":"73","author":"Lei","year":"2021","unstructured":"Lei XSong SLi XGeng C & Wang C2021Excessive body fat at a young age increases the risk of colorectal cancer: a systematic review and meta-analysis. Nutrition and Cancer731601\u20131612. (https:\/\/doi.org\/10.1080\/01635581.2020.1804951)"},{"key":"bib66","series-title":"Journal of Biological Chemistry","first-page":"47469","article-title":"Stimulation of the Raf\/MEK\/ERK cascade is necessary and sufficient for activation and Thr-160 phosphorylation of a nuclear-targeted CDK2","volume":"277","author":"Lents","year":"2002","unstructured":"Lents NHKeenan SMBellone C & Baldassare JJ2002Stimulation of the Raf\/MEK\/ERK cascade is necessary and sufficient for activation and Thr-160 phosphorylation of a nuclear-targeted CDK2. Journal of Biological Chemistry27747469\u201347475. (https:\/\/doi.org\/10.1074\/jbc.M207425200)"},{"key":"bib67","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"4712","article-title":"Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation","volume":"85","author":"Leung","year":"2000","unstructured":"Leung KCDoyle NBallesteros MWaters MJ & Ho KK2000Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation. Journal of Clinical Endocrinology and Metabolism854712\u20134720. (https:\/\/doi.org\/10.1210\/jcem.85.12.7017)"},{"key":"bib68","series-title":"American Journal of Gastroenterology","first-page":"2173","article-title":"Association of body mass index with risk of early-onset colorectal cancer: systematic review and meta-analysis","volume":"116","author":"Li","year":"2021","unstructured":"Li HBoakye DChen XHoffmeister M & Brenner H2021Association of body mass index with risk of early-onset colorectal cancer: systematic review and meta-analysis. American Journal of Gastroenterology1162173\u20132183. (https:\/\/doi.org\/10.14309\/ajg.0000000000001393)"},{"key":"bib69","series-title":"Nature Medicine","first-page":"1941","article-title":"Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce","volume":"27","author":"Li","year":"2021","unstructured":"Li QHagberg CESilva Cascales HLang SHyv\u00f6nen MTSalehzadeh FChen PAlexandersson ITerezaki EHarms MJ, 2021Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. Nature Medicine271941\u20131953. (https:\/\/doi.org\/10.1038\/s41591-021-01501-8)"},{"key":"bib70","series-title":"Medicine (Baltimore)","article-title":"The association between BMI and kidney cancer risk: an updated dose-response meta-analysis in accordance with PRISMA guideline","volume":"97","author":"Liu","year":"2018","unstructured":"Liu XSun QHou HZhu KWang QLiu HZhang QJi L & Li D2018The association between BMI and kidney cancer risk: an updated dose-response meta-analysis in accordance with PRISMA guideline. Medicine (Baltimore)97 e12860. (https:\/\/doi.org\/10.1097\/MD.0000000000012860)"},{"key":"bib71","series-title":"Journal of Clinical Oncology","first-page":"4249","article-title":"Association of obesity-related metabolic disruptions with cancer risk and outcome","volume":"34","author":"Lohmann","year":"2016","unstructured":"Lohmann AEGoodwin PJChlebowski RTPan KStambolic V & Dowling RJO2016Association of obesity-related metabolic disruptions with cancer risk and outcome. Journal of Clinical Oncology344249\u20134255. (https:\/\/doi.org\/10.1200\/JCO.2016.69.6187)"},{"key":"bib72","series-title":"Journal of the National Cancer Institute","first-page":"1465","article-title":"Association of obesity with breast cancer outcome in relation to cancer subtypes: a meta-analysis","volume":"113","author":"Lohmann","year":"2021","unstructured":"Lohmann AESoldera SVPimentel IRibnikar DEnnis MAmir E & Goodwin PJ2021Association of obesity with breast cancer outcome in relation to cancer subtypes: a meta-analysis. Journal of the National Cancer Institute1131465\u20131475. (https:\/\/doi.org\/10.1093\/jnci\/djab023)"},{"key":"bib73","series-title":"Nutrition and Metabolism","article-title":"High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications","volume":"13","author":"Lozano","year":"2016","unstructured":"Lozano IVan der Werf RBietiger WSeyfritz EPeronet CPinget MJeandidier NMaillard EMarchioni ESigrist S, 2016High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications. Nutrition and Metabolism13 15. (https:\/\/doi.org\/10.1186\/s12986-016-0074-1)"},{"key":"bib74","series-title":"Molecular Metabolism","article-title":"Testing the carbohydrate-insulin model in mice: the importance of distinguishing primary hyperinsulinemia from insulin resistance and metabolic dysfunction","volume":"35","author":"Ludwig","year":"2020","unstructured":"Ludwig DSEbbeling CBBikman BT & Johnson JD2020Testing the carbohydrate-insulin model in mice: the importance of distinguishing primary hyperinsulinemia from insulin resistance and metabolic dysfunction. Molecular Metabolism35 100960. (https:\/\/doi.org\/10.1016\/j.molmet.2020.02.003)"},{"key":"bib75","series-title":"Journal of Cellular Physiology","first-page":"654","article-title":"Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer","volume":"202","author":"Macheda","year":"2005","unstructured":"Macheda MLRogers S & Best JD2005Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. Journal of Cellular Physiology202654\u2013662. (https:\/\/doi.org\/10.1002\/jcp.20166)"},{"key":"bib76","series-title":"Advances in Biological Regulation","first-page":"1","article-title":"An expanding role for RAS GTPase activating proteins (RAS GAPs) in cancer","volume":"55","author":"Maertens","year":"2014","unstructured":"Maertens O & Cichowski K2014An expanding role for RAS GTPase activating proteins (RAS GAPs) in cancer. Advances in Biological Regulation551\u201314. (https:\/\/doi.org\/10.1016\/j.jbior.2014.04.002)"},{"key":"bib77","series-title":"Molecular Endocrinology","first-page":"734","article-title":"Different ligand affinities of the two human insulin receptor splice variants are reflected in parallel changes in sensitivity for insulin action","volume":"5","author":"McClain","year":"1991","unstructured":"McClain DA1991Different ligand affinities of the two human insulin receptor splice variants are reflected in parallel changes in sensitivity for insulin action. Molecular Endocrinology5734\u2013739. (https:\/\/doi.org\/10.1210\/mend-5-5-734)"},{"key":"bib78","series-title":"Endocrine","first-page":"478","article-title":"Obesity, metabolic syndrome, and cancer: pathophysiological and therapeutic associations","volume":"74","author":"Mili","year":"2021","unstructured":"Mili NPaschou SAGoulis DGDimopoulos MALambrinoudaki I & Psaltopoulou T2021Obesity, metabolic syndrome, and cancer: pathophysiological and therapeutic associations. Endocrine74478\u2013497. (https:\/\/doi.org\/10.1007\/s12020-021-02884-x)"},{"key":"bib79","series-title":"Cancer Causes and Control","first-page":"537","article-title":"Joint exposure to smoking, excessive weight, and physical inactivity and survival of ovarian cancer patients, evidence from the Ovarian Cancer Association Consortium","volume":"30","author":"Minlikeeva","year":"2019","unstructured":"Minlikeeva ANCannioto RJensen AKjaer SKJordan SJDiergaarde BSzender JBOdunsi KAlmohanna HMayor P, 2019Joint exposure to smoking, excessive weight, and physical inactivity and survival of ovarian cancer patients, evidence from the Ovarian Cancer Association Consortium. Cancer Causes and Control30537\u2013547. (https:\/\/doi.org\/10.1007\/s10552-019-01157-3)"},{"key":"bib80","series-title":"Nutrients","article-title":"Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases","volume":"12","author":"Mirabelli","year":"2020","unstructured":"Mirabelli MChiefari EArcidiacono BCorigliano DMBrunetti FSMaggisano VRusso DFoti DP & Brunetti A2020Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases. Nutrients121066. (https:\/\/doi.org\/10.3390\/nu12041066)"},{"key":"bib81","series-title":"Journal of Lipid Research","first-page":"611","article-title":"Lipid rafts as signaling hubs in cancer cell survival\/death and invasion: implications in tumor progression and therapy: thematic Review Series: biology of Lipid Rafts","volume":"61","author":"Mollinedo","year":"2020","unstructured":"Mollinedo F & Gajate C2020Lipid rafts as signaling hubs in cancer cell survival\/death and invasion: implications in tumor progression and therapy: thematic Review Series: biology of Lipid Rafts. Journal of Lipid Research61611\u2013635. (https:\/\/doi.org\/10.1194\/jlr.TR119000439)"},{"key":"bib82","series-title":"EMBO Journal","first-page":"2409","article-title":"Functionally distinct insulin receptors generated by tissue-specific alternative splicing","volume":"9","author":"Mosthaf","year":"1990","unstructured":"Mosthaf LGrako KDull TJCoussens LUllrich A & McClain DA1990Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO Journal92409\u20132413. (https:\/\/doi.org\/10.1002\/j.1460-2075.1990.tb07416.x)"},{"key":"bib83","series-title":"International Journal of Obesity and Related Metabolic Disorders","first-page":"355","article-title":"Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone","volume":"21","author":"Nam","year":"1997","unstructured":"Nam SYLee EJKim KRCha BSSong YDLim SKLee HC & Huh KB1997Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. International Journal of Obesity and Related Metabolic Disorders21355\u2013359. (https:\/\/doi.org\/10.1038\/sj.ijo.0800412)"},{"key":"bib84","series-title":"Clinical Nutrition","first-page":"1496","article-title":"The association between fat mass and the risk of breast cancer: a systematic review and meta-analysis","volume":"38","author":"Namazi","year":"2019","unstructured":"Namazi NIrandoost PHeshmati JLarijani B & Azadbakht L2019The association between fat mass and the risk of breast cancer: a systematic review and meta-analysis. Clinical Nutrition381496\u20131503. (https:\/\/doi.org\/10.1016\/j.clnu.2018.09.013)"},{"key":"bib85","series-title":"International Journal of Oncology","first-page":"2319","article-title":"The Akt pathway in oncology therapy and beyond (Review)","volume":"53","author":"Nitulescu","year":"2018","unstructured":"Nitulescu GMVan De Venter MNitulescu GUngurianu AJuzenas PPeng QOlaru OTGr\u0103dinaru DTsatsakis ATsoukalas D, 2018The Akt pathway in oncology therapy and beyond (Review). International Journal of Oncology532319\u20132331. (https:\/\/doi.org\/10.3892\/ijo.2018.4597)"},{"key":"bib86","series-title":"Cancer Research","first-page":"741","article-title":"Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes","volume":"70","author":"Novosyadlyy","year":"2010","unstructured":"Novosyadlyy RLann DEVijayakumar ARowzee ALazzarino DAFierz YCarboni JMGottardis MMPennisi PAMolinolo AA, 2010Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes. Cancer Research70741\u2013751. (https:\/\/doi.org\/10.1158\/0008-5472.CAN-09-2141)"},{"key":"bib87","series-title":"World Journal of Surgery","first-page":"2805","article-title":"Association of BMI with clinicopathological features of papillary thyroid cancer: a systematic review and meta-analysis","volume":"45","author":"O\u2019Neill","year":"2021","unstructured":"O\u2019Neill RJAbd Elwahab SKerin MJ & Lowery AJ2021Association of BMI with clinicopathological features of papillary thyroid cancer: a systematic review and meta-analysis. World Journal of Surgery452805\u20132815. (https:\/\/doi.org\/10.1007\/s00268-021-06193-2)"},{"key":"bib88","series-title":"Clinical Gastroenterology and Hepatology","first-page":"1229","article-title":"Risk factors for early-onset colorectal cancer: a systematic review and meta-analysis","volume":"20","author":"O\u2019Sullivan","year":"2022","unstructured":"O\u2019Sullivan DESutherland RLTown SChow KFan JForbes NHeitman SJHilsden RJ & Brenner DR2022Risk factors for early-onset colorectal cancer: a systematic review and meta-analysis. Clinical Gastroenterology and Hepatology201229\u20131240.e5. (https:\/\/doi.org\/10.1016\/j.cgh.2021.01.037)"},{"key":"bib89","series-title":"Current Diabetes Reports","first-page":"213","article-title":"The links between insulin resistance, diabetes, and cancer","volume":"13","author":"Orgel","year":"2013","unstructured":"Orgel E & Mittelman SD2013The links between insulin resistance, diabetes, and cancer. Current Diabetes Reports13213\u2013222. (https:\/\/doi.org\/10.1007\/s11892-012-0356-6)"},{"key":"bib90","series-title":"Frontiers in Molecular Biosciences","article-title":"Divergent mechanisms activating RAS and small GTPases through post-translational modification","volume":"8","author":"Osaka","year":"2021","unstructured":"Osaka NHirota YIto DIkeda YKamata RFujii YChirasani VRCampbell SLTakeuchi KSenda T, 2021Divergent mechanisms activating RAS and small GTPases through post-translational modification. Frontiers in Molecular Biosciences8 707439. (https:\/\/doi.org\/10.3389\/fmolb.2021.707439)"},{"key":"bib91","series-title":"Journal of Biological Chemistry","first-page":"42178","article-title":"Differential gene expression induced by insulin and insulin-like growth factor-II through the insulin receptor isoform A","volume":"278","author":"Pandini","year":"2003","unstructured":"Pandini GMedico EConte ESciacca LVigneri R & Belfiore A2003Differential gene expression induced by insulin and insulin-like growth factor-II through the insulin receptor isoform A. Journal of Biological Chemistry27842178\u201342189. (https:\/\/doi.org\/10.1074\/jbc.M304980200)"},{"key":"bib92","series-title":"Nature Reviews. Endocrinology","first-page":"455","article-title":"Obesity and cancer--mechanisms underlying tumour progression and recurrence","volume":"10","author":"Park","year":"2014","unstructured":"Park JMorley TSKim MClegg DJ & Scherer PE2014Obesity and cancer--mechanisms underlying tumour progression and recurrence. Nature Reviews. Endocrinology10455\u2013465. (https:\/\/doi.org\/10.1038\/nrendo.2014.94)"},{"key":"bib93","series-title":"Cancer Metastasis Reviews","first-page":"517","article-title":"Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases","volume":"41","author":"Pellegata","year":"2022","unstructured":"Pellegata NSBerriel Diaz MRohm M & Herzig S2022Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases. Cancer Metastasis Reviews41517\u2013547. (https:\/\/doi.org\/10.1007\/s10555-022-10058-y)"},{"key":"bib94","series-title":"Frontiers in Endocrinology (Lausanne)","article-title":"Insulin receptor isoform variations in prostate cancer cells","volume":"7","author":"Perks","year":"2016","unstructured":"Perks CMZielinska HAWang JJarrett CFrankow ALadomery MRBahl ARhodes AOxley J & Holly JMP2016Insulin receptor isoform variations in prostate cancer cells. Frontiers in Endocrinology (Lausanne)7 132. (https:\/\/doi.org\/10.3389\/fendo.2016.00132)"},{"key":"bib95","series-title":"Current Opinion in Endocrinology, Diabetes, and Obesity","first-page":"307","article-title":"Growth hormone and cancer: an update on progress","volume":"20","author":"Perry","year":"2013","unstructured":"Perry JKLiu DXWu ZSZhu T & Lobie PE2013Growth hormone and cancer: an update on progress. Current Opinion in Endocrinology, Diabetes, and Obesity20307\u2013313. (https:\/\/doi.org\/10.1097\/MED.0b013e328363183a)"},{"key":"bib96","series-title":"Acta Diabetologica","first-page":"421","article-title":"Insulin resistance\/hyperinsulinemia and cancer mortality: the Cremona study at the 15th year of follow-up","volume":"49","author":"Perseghin","year":"2012","unstructured":"Perseghin GCalori GLattuada GRagogna FDugnani EGarancini MPCrosignani PVilla MBosi ERuotolo G, 2012Insulin resistance\/hyperinsulinemia and cancer mortality: the Cremona study at the 15th year of follow-up. Acta Diabetologica49421\u2013428. (https:\/\/doi.org\/10.1007\/s00592-011-0361-2)"},{"key":"bib97","series-title":"JAMA Network Open","article-title":"Association of obesity with survival outcomes in patients with cancer: A systematic review and meta-analysis","volume":"4","author":"Petrelli","year":"2021","unstructured":"Petrelli FCortellini AIndini ATomasello GGhidini MNigro OSalati MDottorini LIaculli AVarricchio A, 2021Association of obesity with survival outcomes in patients with cancer: A systematic review and meta-analysis. JAMA Network Open4 e213520. (https:\/\/doi.org\/10.1001\/jamanetworkopen.2021.3520)"},{"key":"bib98","series-title":"American Journal of Gastroenterology","first-page":"1494","article-title":"Body mass index, diabetes and intrahepatic cholangiocarcinoma risk: the liver cancer pooling project and meta-analysis","volume":"113","author":"Petrick","year":"2018","unstructured":"Petrick JLThistle JEZeleniuch-Jacquotte AZhang XWactawski-Wende JVan Dyke ALStampfer MJSinha RSesso HDSchairer C, 2018Body mass index, diabetes and intrahepatic cholangiocarcinoma risk: the liver cancer pooling project and meta-analysis. American Journal of Gastroenterology1131494\u20131505. (https:\/\/doi.org\/10.1038\/s41395-018-0207-4)"},{"key":"bib99","series-title":"Nature Reviews. Cancer","first-page":"915","article-title":"Insulin and insulin-like growth factor signalling in neoplasia","volume":"8","author":"Pollak","year":"2008","unstructured":"Pollak M2008Insulin and insulin-like growth factor signalling in neoplasia. Nature Reviews. Cancer8915\u2013928. (https:\/\/doi.org\/10.1038\/nrc2536)"},{"key":"bib100","series-title":"Journal of Clinical Investigation","first-page":"442","article-title":"Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects","volume":"81","author":"Polonsky","year":"1988","unstructured":"Polonsky KSGiven BD & Van Cauter E1988Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. Journal of Clinical Investigation81442\u2013448. (https:\/\/doi.org\/10.1172\/JCI113339)"},{"key":"bib101","series-title":"Cell Death and Disease","article-title":"Obesity and cancer, a case for insulin signaling","volume":"6","author":"Poloz","year":"2015","unstructured":"Poloz Y & Stambolic V2015Obesity and cancer, a case for insulin signaling. Cell Death and Disease6 e2037. (https:\/\/doi.org\/10.1038\/cddis.2015.381)"},{"key":"bib102","series-title":"Cancer Research","first-page":"2969","article-title":"The frequency of ras mutations in cancer","volume":"80","author":"Prior","year":"2020","unstructured":"Prior IAHood FE & Hartley JL2020The frequency of ras mutations in cancer. Cancer Research802969\u20132974. (https:\/\/doi.org\/10.1158\/0008-5472.CAN-19-3682)"},{"key":"bib103","series-title":"International Journal of Molecular Sciences","article-title":"Role of insulin in health and disease: an update","volume":"22","author":"Rahman","year":"2021","unstructured":"Rahman MSHossain KSDas SKundu SAdegoke EORahman MAHannan MAUddin MJ & Pang MG2021Role of insulin in health and disease: an update. International Journal of Molecular Sciences226403. (https:\/\/doi.org\/10.3390\/ijms22126403)"},{"key":"bib104","series-title":"Journal of Endocrinology","first-page":"275","article-title":"Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte","volume":"230","author":"Rajan","year":"2016","unstructured":"Rajan SShankar KBeg MVarshney SGupta ASrivastava AKumar DMishra RKHussain ZGayen JR, 2016Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte. Journal of Endocrinology230275\u2013290. (https:\/\/doi.org\/10.1530\/JOE-16-0099)"},{"key":"bib105","series-title":"iScience","article-title":"A non-canonical function of BMAL1 metabolically limits obesity-promoted triple-negative breast cancer","volume":"23","author":"Ramos","year":"2020","unstructured":"Ramos CAOuyang CQi YChung YCheng CTLaBarge MASeewaldt VL & Ann DK2020A non-canonical function of BMAL1 metabolically limits obesity-promoted triple-negative breast cancer. iScience23 100839. (https:\/\/doi.org\/10.1016\/j.isci.2020.100839)"},{"key":"bib106","series-title":"New England Journal of Medicine","first-page":"1367","article-title":"The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador","volume":"323","author":"Rosenbloom","year":"1990","unstructured":"Rosenbloom ALGuevara Aguirre JRosenfeld RG & Fielder PJ1990The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador. New England Journal of Medicine3231367\u20131374. (https:\/\/doi.org\/10.1056\/NEJM199011153232002)"},{"key":"bib107","series-title":"Endocrine Reviews","first-page":"369","article-title":"Growth hormone (GH) insensitivity due to primary GH receptor deficiency","volume":"15","author":"Rosenfeld","year":"1994","unstructured":"Rosenfeld RGRosenbloom AL & Guevara-Aguirre J1994Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocrine Reviews15369\u2013390. (https:\/\/doi.org\/10.1210\/edrv-15-3-369)"},{"key":"bib108","series-title":"Cancer Treatment Reviews","first-page":"98","article-title":"Challenges and perspectives in the treatment of diabetes associated breast cancer","volume":"70","author":"Samuel","year":"2018","unstructured":"Samuel SMVarghese EVarghese S & B\u00fcsselberg D2018Challenges and perspectives in the treatment of diabetes associated breast cancer. Cancer Treatment Reviews7098\u2013111. (https:\/\/doi.org\/10.1016\/j.ctrv.2018.08.004)"},{"key":"bib109","series-title":"Cancer Epidemiology, Biomarkers and Prevention","first-page":"2093","article-title":"Reduced insulin-like growth factor I receptor and altered insulin receptor isoform mRNAs in normal mucosa predict colorectal adenoma risk","volume":"23","author":"Santoro","year":"2014","unstructured":"Santoro MAAndres SFGalanko JASandler RSKeku TO & Lund PK2014Reduced insulin-like growth factor I receptor and altered insulin receptor isoform mRNAs in normal mucosa predict colorectal adenoma risk. Cancer Epidemiology, Biomarkers and Prevention232093\u20132100. (https:\/\/doi.org\/10.1158\/1055-9965.EPI-14-0177)"},{"key":"bib110","series-title":"Frontiers in Oncology","article-title":"Obesity, type 2 diabetes, and cancer risk","volume":"10","author":"Scully","year":"2021","unstructured":"Scully TEttela ALeRoith D & Gallagher EJ2021Obesity, type 2 diabetes, and cancer risk. Frontiers in Oncology10 615375. (https:\/\/doi.org\/10.3389\/fonc.2020.615375)"},{"key":"bib111","series-title":"Medicine (Baltimore)","article-title":"Associations between body mass index and the risk of mortality from lung cancer: a dose-response PRISMA-compliant meta-analysis of prospective cohort studies","volume":"96","author":"Shen","year":"2017","unstructured":"Shen NFu PCui BBu CY & Bi JW2017Associations between body mass index and the risk of mortality from lung cancer: a dose-response PRISMA-compliant meta-analysis of prospective cohort studies. Medicine (Baltimore)96 e7721. (https:\/\/doi.org\/10.1097\/MD.0000000000007721)"},{"key":"bib112","series-title":"Systematic Reviews","article-title":"Associating the risk of three urinary cancers with obesity and overweight: an overview with evidence mapping of systematic reviews","volume":"10","author":"Shi","year":"2021","unstructured":"Shi JZhao LGao YNiu MYan MChen YSong ZMa XWang P & Tian J2021Associating the risk of three urinary cancers with obesity and overweight: an overview with evidence mapping of systematic reviews. Systematic Reviews10 58. (https:\/\/doi.org\/10.1186\/s13643-021-01606-8)"},{"key":"bib113","series-title":"Antioxidants (Basel)","article-title":"The impact of oxidative stress and AKT pathway on cancer cell functions and its application to natural products","volume":"11","author":"Shiau","year":"2022","unstructured":"Shiau JPChuang YTTang JYYang KHChang FRHou MFYen CY & Chang HW2022The impact of oxidative stress and AKT pathway on cancer cell functions and its application to natural products. Antioxidants (Basel)111845. (https:\/\/doi.org\/10.3390\/antiox11091845)"},{"key":"bib114","series-title":"Thyroid","first-page":"306","article-title":"Body mass index and thyroid cancer risk: a pooled analysis of half a million men and women in the Asia cohort consortium","volume":"32","author":"Shin","year":"2022","unstructured":"Shin ACho SJang DAbe SKSaito ERahman MSIslam MRSawada NShu XOKoh WP, 2022Body mass index and thyroid cancer risk: a pooled analysis of half a million men and women in the Asia cohort consortium. Thyroid32306\u2013314. (https:\/\/doi.org\/10.1089\/thy.2021.0445)"},{"key":"bib115","series-title":"Targeted Oncology","first-page":"571","article-title":"Insulin-like growth factor (IGF) pathway targeting in cancer: role of the IGF axis and opportunities for future combination studies","volume":"12","author":"Simpson","year":"2017","unstructured":"Simpson APetnga WMacaulay VMWeyer-Czernilofsky U & Bogenrieder T2017Insulin-like growth factor (IGF) pathway targeting in cancer: role of the IGF axis and opportunities for future combination studies. Targeted Oncology12571\u2013597. (https:\/\/doi.org\/10.1007\/s11523-017-0514-5)"},{"key":"bib116","series-title":"Scientific Reports","article-title":"Body mass index and cancer risk in patients with type 2 diabetes: a dose-response meta-analysis of cohort studies","volume":"11","author":"Soltani","year":"2021","unstructured":"Soltani SAbdollahi SAune D & Jayedi A2021Body mass index and cancer risk in patients with type 2 diabetes: a dose-response meta-analysis of cohort studies. Scientific Reports11 2479. (https:\/\/doi.org\/10.1038\/s41598-021-81671-0)"},{"key":"bib117","series-title":"EBiomedicine","first-page":"14","article-title":"Obesity and cancer: existing and new hypotheses for a causal connection","volume":"30","author":"Stone","year":"2018","unstructured":"Stone TWMcPherson M & Gail Darlington L2018Obesity and cancer: existing and new hypotheses for a causal connection. EBiomedicine3014\u201328. (https:\/\/doi.org\/10.1016\/j.ebiom.2018.02.022)"},{"key":"bib118","series-title":"American Journal of Cancer Research","first-page":"2334","article-title":"Association of insulin resistance with breast, ovarian, endometrial and cervical cancers in non-diabetic women","volume":"6","author":"Sun","year":"2016","unstructured":"Sun WLu JWu SBi YMu YZhao JLiu CChen LShi LLi Q, 2016Association of insulin resistance with breast, ovarian, endometrial and cervical cancers in non-diabetic women. American Journal of Cancer Research62334\u20132344."},{"key":"bib119","series-title":"Obesity","first-page":"1724","article-title":"Health consequences of obesity and projected future obesity health burden in China","volume":"30","author":"Sun","year":"2022","unstructured":"Sun XYan AFShi ZZhao BYan NLi KGao LXue HPeng WCheskin LJ, 2022Health consequences of obesity and projected future obesity health burden in China. Obesity301724\u20131751. (https:\/\/doi.org\/10.1002\/oby.23472)"},{"key":"bib120","series-title":"Journal of the Endocrine Society","first-page":"1727","article-title":"Hyperinsulinemia: an early indicator of metabolic dysfunction","volume":"3","author":"Thomas","year":"2019","unstructured":"Thomas DDCorkey BEIstfan NW & Apovian CM2019Hyperinsulinemia: an early indicator of metabolic dysfunction. Journal of the Endocrine Society31727\u20131747. (https:\/\/doi.org\/10.1210\/js.2019-00065)"},{"key":"bib121","series-title":"Journal of Gastroenterology and Hepatology","first-page":"730","article-title":"Cumulative evidence for the relationship between body mass index and the risk of esophageal cancer: an updated meta-analysis with evidence from 25 observational studies","volume":"35","author":"Tian","year":"2020","unstructured":"Tian JZuo CLiu GChe PLi GLi X & Chen H2020Cumulative evidence for the relationship between body mass index and the risk of esophageal cancer: an updated meta-analysis with evidence from 25 observational studies. Journal of Gastroenterology and Hepatology35730\u2013743. (https:\/\/doi.org\/10.1111\/jgh.14917)"},{"key":"bib122","series-title":"PNAS","first-page":"14800","article-title":"The mutation rate and cancer","volume":"93","author":"Tomlinson","year":"1996","unstructured":"Tomlinson IPNovelli MR & Bodmer WF1996The mutation rate and cancer. PNAS9314800\u201314803. (https:\/\/doi.org\/10.1073\/pnas.93.25.14800)"},{"key":"bib123","series-title":"Molecular Cell","first-page":"758","article-title":"Cyclin D-Cdk4,6 drives cell-cycle progression via the retinoblastoma protein\u2019s C-terminal helix","volume":"74","author":"Topacio","year":"2019","unstructured":"Topacio BRZatulovskiy ECristea SXie STambo CSRubin SMSage JK\u00f5ivom\u00e4gi M & Skotheim JM2019Cyclin D-Cdk4,6 drives cell-cycle progression via the retinoblastoma protein\u2019s C-terminal helix. Molecular Cell74758\u2013770.e4. (https:\/\/doi.org\/10.1016\/j.molcel.2019.03.020)"},{"key":"bib124","series-title":"Journal of Biomedical Science","article-title":"Akt: a key transducer in cancer","volume":"29","author":"Tsai","year":"2022","unstructured":"Tsai PJLai YHManne RKTsai YSSarbassov D & Lin HK2022Akt: a key transducer in cancer. Journal of Biomedical Science29 76. (https:\/\/doi.org\/10.1186\/s12929-022-00860-9)"},{"key":"bib125","series-title":"International Journal of Cancer","first-page":"102","article-title":"Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: a population-based observational study","volume":"141","author":"Tsujimoto","year":"2017","unstructured":"Tsujimoto TKajio H & Sugiyama T2017Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: a population-based observational study. International Journal of Cancer141102\u2013111. (https:\/\/doi.org\/10.1002\/ijc.30729)"},{"key":"bib126","series-title":"Nature","first-page":"756","article-title":"Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes","volume":"313","author":"Ullrich","year":"1985","unstructured":"Ullrich ABell JRChen EYHerrera RPetruzzelli LMDull TJGray ACoussens LLiao YC & Tsubokawa M1985Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature313756\u2013761. (https:\/\/doi.org\/10.1038\/313756a0)"},{"key":"bib127","series-title":"Nature Reviews. Immunology","first-page":"641","article-title":"Inflammation and necrosis promote tumour growth","volume":"4","author":"Vakkila","year":"2004","unstructured":"Vakkila J & Lotze MT2004Inflammation and necrosis promote tumour growth. Nature Reviews. Immunology4641\u2013648. (https:\/\/doi.org\/10.1038\/nri1415)"},{"key":"bib128","series-title":"Diabetes","first-page":"2112","article-title":"Obesity is associated with increased basal and postprandial \u03b2-cell insulin secretion even in the absence of insulin resistance","volume":"69","author":"Van Vliet","year":"2020","unstructured":"Van Vliet SKoh H-CEPatterson BWYoshino MLaForest RGropler RJKlein S & Mittendorfer B2020Obesity is associated with increased basal and postprandial \u03b2-cell insulin secretion even in the absence of insulin resistance. Diabetes692112\u20132119. (https:\/\/doi.org\/10.2337\/db20-0377)"},{"key":"bib129","series-title":"Science","first-page":"1029","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","unstructured":"Vander Heiden MGCantley LC & Thompson CB2009Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science3241029\u20131033. (https:\/\/doi.org\/10.1126\/science.1160809)"},{"key":"bib130","series-title":"Journal of Endocrinological Investigation","first-page":"1365","article-title":"Insulin, insulin receptors, and cancer","volume":"39","author":"Vigneri","year":"2016","unstructured":"Vigneri RGoldfine ID & Frittitta L2016Insulin, insulin receptors, and cancer. Journal of Endocrinological Investigation391365\u20131376. (https:\/\/doi.org\/10.1007\/s40618-016-0508-7)"},{"key":"bib131","series-title":"Diabetologia","first-page":"1","article-title":"Fasting proinsulin levels are significantly associated with 20 year cancer mortality rates. The Hoorn Study","volume":"56","author":"Walraven","year":"2013","unstructured":"Walraven Ivan \u2019t Riet EStehouwer CDAPolak BCPMoll ACDekker JMNijpels G. Fasting proinsulin levels are significantly associated with 20 year cancer mortality rates. The Hoorn Study. Diabetologia2013561148\u20131154."},{"key":"bib132","series-title":"PLoS One","article-title":"Overexpression of the insulin receptor isoform A promotes endometrial carcinoma cell growth","volume":"8","author":"Wang","year":"2013","unstructured":"Wang CFZhang GZhao LJQi WJLi XPWang JL & Wei LH2013Overexpression of the insulin receptor isoform A promotes endometrial carcinoma cell growth. PLoS One8 e69001. (https:\/\/doi.org\/10.1371\/journal.pone.0069001)"},{"key":"bib133","series-title":"Journal of Cancer","first-page":"761","article-title":"Role of tumor microenvironment in tumorigenesis","volume":"8","author":"Wang","year":"2017","unstructured":"Wang MZhao JZhang LWei FLian YWu YGong ZZhang SZhou JCao K, 2017Role of tumor microenvironment in tumorigenesis. Journal of Cancer8761\u2013773. (https:\/\/doi.org\/10.7150\/jca.17648)"},{"key":"bib134","series-title":"Gynecologic Oncology","first-page":"734","article-title":"Mitogenic and anti-apoptotic effects of insulin in endometrial cancer are phosphatidylinositol 3-kinase\/Akt dependent","volume":"125","author":"Wang","year":"2012","unstructured":"Wang YHua STian WZhang LZhao JZhang HZhang W & Xue F2012Mitogenic and anti-apoptotic effects of insulin in endometrial cancer are phosphatidylinositol 3-kinase\/Akt dependent. Gynecologic Oncology125734\u2013741. (https:\/\/doi.org\/10.1016\/j.ygyno.2012.03.012)"},{"key":"bib135","series-title":"Oncologist","first-page":"556","article-title":"Obesity and cancer","volume":"15","author":"Wolin","year":"2010","unstructured":"Wolin KYCarson K & Colditz GA2010Obesity and cancer. Oncologist15556\u2013565. (https:\/\/doi.org\/10.1634\/theoncologist.2009-0285)"},{"key":"bib136","series-title":"Journal of Hematology and Oncology","article-title":"Cancer-associated adipocytes: key players in breast cancer progression","volume":"12","year":"2019","unstructured":"Wu Q, Li B, Li Z, Li J, Sun S & Sun S2019Cancer-associated adipocytes: key players in breast cancer progression. Journal of Hematology and Oncology12 95. (https:\/\/doi.org\/10.1186\/s13045-019-0778-6)"},{"key":"bib137","series-title":"Signal Transduction and Targeted Therapy","article-title":"Crosstalk between circRNAs and the PI3K\/AKT signaling pathway in cancer progression","volume":"6","author":"Xue","year":"2021","unstructured":"Xue CLi GLu J & Li L2021Crosstalk between circRNAs and the PI3K\/AKT signaling pathway in cancer progression. Signal Transduction and Targeted Therapy6 400. (https:\/\/doi.org\/10.1038\/s41392-021-00788-w)"},{"key":"bib138","series-title":"Endocrinology","first-page":"2058","article-title":"Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells","volume":"129","author":"Yamaguchi","year":"1991","unstructured":"Yamaguchi YFlier JSYokota ABenecke HBacker JM & Moller DE1991Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells. Endocrinology1292058\u20132066. (https:\/\/doi.org\/10.1210\/endo-129-4-2058)"},{"key":"bib139","series-title":"Nutrition and Cancer","first-page":"1085","article-title":"Excess body weight and the risk of liver cancer: systematic review and a meta-analysis of cohort studies","volume":"72","author":"Yang","year":"2020","unstructured":"Yang CLu YXia HLiu HPan DYang X & Sun G2020Excess body weight and the risk of liver cancer: systematic review and a meta-analysis of cohort studies. Nutrition and Cancer721085\u20131097. (https:\/\/doi.org\/10.1080\/01635581.2019.1664602)"},{"key":"bib140","series-title":"Diabetes and Metabolism Journal","first-page":"285","article-title":"Hyperinsulinemia in obesity, inflammation, and cancer","volume":"45","author":"Zhang","year":"2021","unstructured":"Zhang AMYWellberg EAKopp JL & Johnson JD2021Hyperinsulinemia in obesity, inflammation, and cancer. Diabetes and Metabolism Journal45285\u2013311. (https:\/\/doi.org\/10.4093\/dmj.2020.0250)"},{"key":"bib141","series-title":"Nature Medicine","first-page":"812","article-title":"Fen1 mutations result in autoimmunity, chronic inflammation and cancers","volume":"13","author":"Zheng","year":"2007","unstructured":"Zheng LDai HZhou MLi MSingh PQiu JTsark WHuang QKernstine KZhang X, 2007Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Nature Medicine13812\u2013819. (https:\/\/doi.org\/10.1038\/nm1599)"},{"key":"bib142","series-title":"Journal of Cell Biology","first-page":"483","article-title":"Akt regulates cell survival and apoptosis at a postmitochondrial level","volume":"151","author":"Zhou","year":"2000","unstructured":"Zhou HLi XMMeinkoth J & Pittman RN2000Akt regulates cell survival and apoptosis at a postmitochondrial level. Journal of Cell Biology151483\u2013494. (https:\/\/doi.org\/10.1083\/jcb.151.3.483)"},{"key":"bib143","series-title":"BMC Cancer","article-title":"Body mass index and lung cancer risk in never smokers: a meta-analysis","volume":"18","author":"Zhu","year":"2018","unstructured":"Zhu H & Zhang S2018Body mass index and lung cancer risk in never smokers: a meta-analysis. BMC Cancer18 635. 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