Diabetes and Cancer

Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis; 2) risk factors common to both diabetes and cancer; 3) possible biologic links between diabetes and cancer risk; and 4) whether diabetes treatments influence the risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed. CA Cancer J Clin 2010. © 2010 American Cancer Society, Inc.

[1]  David M. Sabatini,et al.  Tumours with PI3K activation are resistant to dietary restriction , 2009, Nature.

[2]  J. Shikany,et al.  Dietary carbohydrate, glycemic index, and glycemic load in relation to colorectal cancer risk in the Women’s Health Initiative , 2008, Cancer Causes & Control.

[3]  U. Smith,et al.  Does diabetes therapy influence the risk of cancer? , 2009, Diabetologia.

[4]  R. Glasgow,et al.  Smoking and diabetes. , 2004, Diabetes care.

[5]  Jun Hee Lee,et al.  Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression , 2010, Cell.

[6]  B. Littenberg,et al.  Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System , 2007, BMC medicine.

[7]  G. Landman,et al.  Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes , 2009, Diabetes Care.

[8]  P. Butler.  Insulin Glargine Controversy: A Tribute to the Editorial Team at Diabetologia , 2009, Diabetes.

[9]  H. Gerstein.  Does insulin therapy promote, reduce, or have a neutral effect on cancers? , 2010, JAMA.

[10]  R. Brand,et al.  Elevated insulin receptor content in human breast cancer. , 1990, The Journal of clinical investigation.

[11]  A. Wolff,et al.  Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. , 2008, JAMA.

[12]  B. Spiegelman,et al.  Use of the Peroxisome Proliferator-Activated Receptor (PPAR) γ Ligand Troglitazone as Treatment for Refractory Breast Cancer: A Phase II Study , 2003, Breast Cancer Research and Treatment.

[13]  J. Menéndez,et al.  The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells , 2009, Cell cycle.

[14]  S. Hilsenbeck,et al.  Time-dependence of hazard ratios for prognostic factors in primary breast cancer , 2004, Breast Cancer Research and Treatment.

[15]  S. Haffner,et al.  Waist circumference as the best predictor of noninsulin dependent diabetes mellitus (NIDDM) compared to body mass index, waist/hip ratio and other anthropometric measurements in Mexican Americans--a 7-year prospective study. , 1997, Obesity research.

[16]  C. Friedenreich,et al.  Physical activity and cancer prevention: etiologic evidence and biological mechanisms. , 2002, The Journal of nutrition.

[17]  G. Steineck,et al.  Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden , 2009, Diabetologia.

[18]  J. Arnsten,et al.  Effect of alcohol consumption on diabetes mellitus: a systematic review. , 2004, Annals of internal medicine.

[19]  S. Sorrenti,et al.  The urokinase plasminogen activator system: a target for anti-cancer therapy. , 2009, Current cancer drug targets.

[20]  R. Bergenstal,et al.  Type 2 diabetes: assessing the relative risks and benefits of glucose-lowering medications. , 2010, The American journal of medicine.

[21]  A. Renehan,et al.  Obesity and cancer risk: the role of the insulin–IGF axis , 2006, Trends in Endocrinology & Metabolism.

[22]  Kevin P. High,et al.  15-Deoxy-Δ12,14-prostaglandin J2-induced apoptosis does not require PPARγ in breast cancer cells Published, JLR Papers in Press, August 16, 2002. DOI 10.1194/jlr.M200224-JLR200 , 2002, Journal of Lipid Research.

[23]  C. Currie,et al.  The longest ever randomised controlled trial of insulin glargine: study design and HbA1c findings , 2009, Diabetologia.

[24]  F. Visseren,et al.  Obesity and Cancer: The Role of Dysfunctional Adipose Tissue , 2009, Cancer Epidemiology, Biomarkers & Prevention.

[25]  T. Valle,et al.  Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. , 2001, The New England journal of medicine.

[26]  M. Mathieu,et al.  Insulin receptor expression and clinical outcome in node-negative breast cancer. , 1997, Proceedings of the Association of American Physicians.

[27]  L. Cantley,et al.  Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation , 2009, Science.

[28]  Bolin Liu,et al.  Metformin induces unique biological and molecular responses in triple negative breast cancer cells , 2009, Cell cycle.

[29]  Sui Huang,et al.  PPARγ as a therapeutic target for tumor angiogenesis and metastasis , 2005 .

[30]  K. Straif,et al.  A review of human carcinogens--Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. , 2009, The Lancet. Oncology.

[31]  Sui Huang,et al.  PPARgamma as a therapeutic target for tumor angiogenesis and metastasis. , 2005, Cancer biology & therapy.

[32]  廣畑 富雄,et al.  Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective , 2007 .

[33]  D. Panagiotakos,et al.  Dietary patterns and prevention of type 2 diabetes: from research to clinical practice; a systematic review. , 2009, Current diabetes reviews.

[34]  J. Menéndez,et al.  Genome-wide inhibitory impact of the AMPK activator metformin on [kinesins, tubulins, histones, auroras and polo-like kinases] M-phase cell cycle genes in human breast cancer cells , 2009, Cell cycle.

[35]  M. Jensen,et al.  Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. , 2009, The American journal of medicine.

[36]  F. Hu,et al.  Glycemic index, glycemic load, and cereal fiber intake and risk of type 2 diabetes in US black women. , 2007, Archives of internal medicine.

[37]  Graham A Colditz,et al.  Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. , 2006, Journal of the National Cancer Institute.

[38]  M. Cazzaniga,et al.  Is it Time to Test Metformin in Breast Cancer Clinical Trials? , 2009, Cancer Epidemiology Biomarkers & Prevention.

[39]  M. Abdul-Ghani,et al.  High frequency of pre-diabetes, undiagnosed diabetes and metabolic syndrome among overweight Arabs in Israel. , 2005, The Israel Medical Association journal : IMAJ.

[40]  J. Wylie-Rosett,et al.  Nutritional Management of Diabetes , 2009 .

[41]  S. Hankinson,et al.  Racial Differences in Premenopausal Endogenous Hormones , 2005, Cancer Epidemiology Biomarkers & Prevention.

[42]  F. Ondrey,et al.  Peroxisome Proliferator-Activated Receptor γ Pathway Targeting in Carcinogenesis: Implications for Chemoprevention , 2009, Clinical Cancer Research.

[43]  N. Sonenberg,et al.  Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. , 2007, Cancer research.

[44]  Graham A Colditz,et al.  Physical activity and survival after colorectal cancer diagnosis. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  Cody Schrank,et al.  American Cancer Society , 2005 .

[46]  H. Colhoun,et al.  Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group , 2009, Diabetologia.

[47]  Do cancer cells care if their host is hungry? , 2009, Cell metabolism.

[48]  Alan D. Lopez,et al.  Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data , 2006, The Lancet.

[49]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[50]  Ralph A. DeFronzo,et al.  From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus , 2009, Diabetes.

[51]  the Scottish Diabetes Research Network Epidemiology Group.  Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group , 2009, Diabetologia.

[52]  W. Willett,et al.  Adult weight change and risk of postmenopausal breast cancer. , 2006, JAMA.

[53]  D. Nathan.  Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A Consensus Statement of the American Diabetes Association and the European Association for the Study of Diabetes , 2009, Diabetes Care.

[54]  L. Shaw,et al.  Expression and function of the insulin receptor substrate proteins in cancer , 2009, Cell Communication and Signaling.

[55]  H. Arnqvist,et al.  Mitogenic Effect of the Insulin Analogue Glargine in Malignant Cells in Comparison with Insulin and IGF-I , 2008, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[56]  L. Hemkens,et al.  Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study , 2009, Diabetologia.

[57]  A. Renehan.  Bariatric surgery, weight reduction, and cancer prevention. , 2009, The Lancet. Oncology.

[58]  E. Gale,et al.  The influence of glucose-lowering therapies on cancer risk in type 2 diabetes , 2009, Diabetologia.

[59]  I-Min Lee,et al.  Physical activity and cancer prevention--data from epidemiologic studies. , 2003, Medicine and science in sports and exercise.

[60]  A. Thor,et al.  Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro , 2009, Cell cycle.

[61]  S. Jabbour.  Primary care physicians and insulin initiation: multiple barriers, lack of knowledge or both? , 2008, International journal of clinical practice.

[62]  M. Pollak,et al.  Insulin analogues and cancer risk: cause for concern or cause célèbre? , 2010, International journal of clinical practice.

[63]  Sharla Montvel-Cohen.  "Search for diabetes in youth". , 2006, Hawaii medical journal.

[64]  J. McGill,et al.  Similar risk of malignancy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: findings from a 5 year randomised, open-label study , 2009, Diabetologia.

[65]  E. Calle,et al.  Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms , 2004, Nature Reviews Cancer.

[66]  P. Mitchell,et al.  Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of observational studies. , 2008, The American journal of clinical nutrition.

[67]  J. Meyerhardt,et al.  Insulin, the insulin-like growth factor axis, and mortality in patients with nonmetastatic colorectal cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002 .

[69]  Jürgen Rehm,et al.  Alcohol as a Risk Factor for Type 2 Diabetes , 2009, Diabetes Care.

[70]  Nahum Sonenberg,et al.  Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. , 2006, Cancer research.

[71]  L. Schäffer,et al.  Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. , 2000, Diabetes.

[72]  M. Schulze,et al.  Body mass index history and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. , 2006, The American journal of clinical nutrition.

[73]  Michael J Thun,et al.  Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. , 2003, The New England journal of medicine.

[74]  R. DePinho,et al.  The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin , 2005, Science.

[75]  J. Stanford,et al.  Metformin use and prostate cancer in Caucasian men: results from a population-based case–control study , 2009, Cancer Causes & Control.

[76]  Lawrence H. Kushi,et al.  Erratum: American Cancer Society guidelines on nutrition and physical activity for cancer prevention: Reducing the risk of cancer with healthy food choices and physical activity (CA - A Cancer Journal for Clinicians (2006) 56, (254-281)) , 2007 .

[77]  N. Legros,et al.  Influence of insulin deprivation on growth of the 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats subjected to alloxan diabetes and food restriction. , 1972, Cancer research.

[78]  H. Masoudi,et al.  Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival. , 2008, Cancer research.

[79]  L. Maile,et al.  Role of the integrin αVβ3 in mediating increased smooth muscle cell responsiveness to IGF-I in response to hyperglycemic stress , 2007 .

[80]  E. Joslin,et al.  Diabetes and cancer. , 1959, The New England journal of medicine.

[81]  J. Halperin,et al.  Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor gamma and mediated by inhibition of translation initiation. , 2001, Cancer research.

[82]  D. Yee,et al.  Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin. , 2007, Cancer research.

[83]  K. Kinzler,et al.  Glucose Deprivation Contributes to the Development of KRAS Pathway Mutations in Tumor Cells , 2009, Science.

[84]  SEARCH DIABETES , 2007, Herz Kardiovaskuläre Erkrankungen.

[85]  V. Ehemann,et al.  Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines. , 2009, Endocrine-related cancer.

[86]  G. Bray,et al.  Reduction in Weight and Cardiovascular Disease Risk Factors in Individuals With Type 2 Diabetes , 2007, Diabetes Care.

[87]  Kevin Struhl,et al.  Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. , 2009, Cancer research.

[88]  Robert H. Bell,et al.  Insulin receptor expression by human prostate cancers , 2009, The Prostate.

[89]  H. Grosse.  [Diabetes and cancer]. , 1956, Deutsche Zeitschrift fur Verdauungs- und Stoffwechselkrankheiten.

[90]  Desmond E. Williams,et al.  The Burden of Diabetes Mellitus Among US Youth: Prevalence Estimates From the SEARCH for Diabetes in Youth Study , 2006, Pediatrics.

[91]  A. Rosenbloom,et al.  Emerging epidemic of type 2 diabetes in youth. , 1999, Diabetes care.

[92]  C. Franceschi,et al.  Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice , 2005, Experimental Gerontology.

[93]  D. Balzi,et al.  Sulphonylureas and cancer: a case–control study , 2008, Acta Diabetologica.

[94]  M. Stampfer,et al.  Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis. , 2008, The Lancet. Oncology.

[95]  S. Majumdar,et al.  Increased Cancer-Related Mortality for Patients With Type 2 Diabetes Who Use Sulfonylureas or Insulin , 2006, Diabetes Care.

[96]  N. Qizilbash,et al.  Cancer risks in thiazolidinedione users compared to other anti‐diabetic agents , 2007, Pharmacoepidemiology and drug safety.

[97]  G. Atsumi,et al.  Magnitude of Peroxisome Proliferator-Activated Receptor-γ Activation is Associated With Important and Seemingly Opposite Biological Responses in Breast Cancer Cells , 2001, Journal of Investigative Medicine.

[98]  Funda Meric-Bernstam,et al.  Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[99]  E. Siegel,et al.  Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[100]  D. Powell,et al.  Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1. , 1991, The Journal of biological chemistry.

[101]  M. Pollak,et al.  Insulin and insulin-like growth factor signalling in neoplasia , 2008, Nature Reviews Cancer.

[102]  Anna Marie Mulligan,et al.  Insulin receptor is an independent predictor of a favorable outcome in early stage breast cancer , 2007, Breast Cancer Research and Treatment.

[103]  Graham A Colditz,et al.  Physical activity and survival after breast cancer diagnosis. , 2004, JAMA.

[104]  Hua Yu,et al.  STATs in cancer inflammation and immunity: a leading role for STAT3 , 2009, Nature Reviews Cancer.

[105]  J. Thorburn,et al.  15-Deoxy-delta12,14-prostaglandin J2-induced apoptosis does not require PPARgamma in breast cancer cells. , 2002, Journal of lipid research.

[106]  C. Roberts,et al.  Differential Activation of Insulin Receptor Substrates 1 and 2 by Insulin-Like Growth Factor-Activated Insulin Receptors , 2007, Molecular and Cellular Biology.

[107]  L. Wagenknecht,et al.  Smoking and incidence of diabetes among U.S. adults: findings from the Insulin Resistance Atherosclerosis Study. , 2005, Diabetes care.

[108]  Dario R Alessi,et al.  Metformin and reduced risk of cancer in diabetic patients , 2005, BMJ : British Medical Journal.

[109]  J. Cornuz,et al.  Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis. , 2007, JAMA.

[110]  H. Werner,et al.  Insulin analogues display IGF‐I‐like mitogenic and anti‐apoptotic activities in cultured cancer cells , 2009, Diabetes/metabolism research and reviews.

[111]  R. Sorelle.  US Department of Health and Human Services gives states wider latitude in choosing services to be covered by Medicaid. , 2001, Circulation.

[112]  L. Tanoue.  Cancer Statistics, 2009 , 2010 .

[113]  A. Morisset,et al.  Prevention of gestational diabetes mellitus: a review of studies on weight management , 2010, Diabetes/metabolism research and reviews.

[114]  F. Ovalle.  Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes: ZODIAC-16 , 2010 .

[115]  M. Plummer,et al.  International agency for research on cancer. , 2020, Archives of pathology.

[116]  B. Zinman,et al.  The impact of diabetes on survival following breast cancer , 2008, Breast Cancer Research and Treatment.

[117]  L. Maile,et al.  Role of the integrin alphaVbeta3 in mediating increased smooth muscle cell responsiveness to IGF-I in response to hyperglycemic stress. , 2007, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[118]  C. Friedenreich,et al.  Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). , 2006, Journal of the National Cancer Institute.

[119]  D. Hum,et al.  Safety issues and prospects for future generations of PPAR modulators. , 2007, Biochimica et biophysica acta.

[120]  K Ohta,et al.  Ligands for peroxisome proliferator-activated receptor gamma inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells. , 2001, The Journal of clinical endocrinology and metabolism.

[121]  M. Rechler,et al.  Insulin rapidly decreases insulin-like growth factor-binding protein-1 gene transcription in streptozotocin-diabetic rats. , 1992, Molecular endocrinology.

[122]  S. Mayne,et al.  Dietary glycemic index, glycemic load, and risk of cancer: a prospective cohort study. , 2008, American journal of epidemiology.

[123]  M. Pollak,et al.  Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth. , 2008, Endocrine-related cancer.

[124]  M. Thun,et al.  American Cancer Society guidelines on nutrition and physical activity for cancer prevention , 2002, CA: a cancer journal for clinicians.

[125]  E. Giovannucci.  Insulin, insulin-like growth factors and colon cancer: a review of the evidence. , 2001, The Journal of nutrition.