Skip to main content
×
Home
    • Aa
    • Aa

Energy balance and cancer: the role of insulin and insulin-like growth factor-I

  • R. Kaaks (a1) and A. Lukanova (a1)
Abstract

Recent theories propose that a Western lifestyle may increase cancer risk through alterations in the metabolism of insulin and insulin-like growth factors (IGF; McKeown-Eyssen, 1994; Giovannucci, 1995; Kaaks, 1996; Werner & LeRoith, 1996). Insulin regulates energy metabolism, and increases the bioactivity of IGF-I, by enhancing its synthesis, and by decreasing several of its binding proteins (IGFBP; IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic processes as a function of available energy and elementary substrates (e.g. amino acids). The anabolic signals by insulin or IGF-I can promote tumour development by inhibiting apoptosis, and by stimulating cell proliferation. Furthermore, both insulin and IGF-I stimulate the synthesis of sex steroids, and inhibit the synthesis of sex hormone-binding globulin (SHBG), a binding protein that regulates the bioavailability of circulating sex steroids to tissues. The present paper reviews epidemiological findings relating the risk of cancers of the colo-rectum, pancreas, breast, endometrium and prostate to body size (obesity, height) and physical activity, and discusses the relationships between obesity and physical activity and plasma levels of insulin, IGF-I and IGFBP. Subsequent sections review epidemiological findings relating cancer risk to indices of chronic hyperinsulinaemia, and to plasma levels of IGF-I and IGFBP. Conclusions are that chronic hyperinsulinaemia may be a cause of cancers of the colon, pancreas and endometrium, and also possibly of the breast. On the other hand, elevated plasma IGF-I, as total concentrations or relative to levels of IGFBP-3, appears to be related to an increased risk of prostate cancer, breast cancer in young women, and possibly colo-rectal cancer. For cancers of the endometrium, breast and prostate, these findings are discussed in the context of relationships between insulin and IGF-I and levels of bioavailable sex steroids.

    • Send article to Kindle

      To send this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Energy balance and cancer: the role of insulin and insulin-like growth factor-I
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Energy balance and cancer: the role of insulin and insulin-like growth factor-I
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Energy balance and cancer: the role of insulin and insulin-like growth factor-I
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Dr R. Kaaks, fax +33 4 72 73 83 61, email kaaks@iarc.fr
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

N Abate (1996) Insulin resistance and obesity. The role of fat distribution pattern. Diabetes Care 19, 292294.

HO Adami , HO Dami , J McLaughlin , A Ekbom , C Berne , D Silverman , D Hacker & I Persson (1991) Cancer risk in patients with diabetes mellitus. Cancer Causes Control 2, 307314.

J Argente , N Caballo , V Barrios , MT Munoz , J Pozo , JA Chowen , G Morande & M Hernandez (1997) Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation. Journal of Clinical Endocrinology and Metabolism 82, 20842092.

T Ayabe , O Tsutsumi , H Sakai , H Yoshikawa , T Yano , F Kurimoto & Y Taketani (1997) Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer. Endocrine Journal 44, 419424.

R Ballard-Barbash (1994) Anthropometry and breast cancer. Body size – a moving target. Cancer 74, 10901100.

P Bang , J Brandt , M Degerblad , G Enberg , L Kaijser , M Thoren & K Hall (1990) Exercise-induced changes in insulin-like growth factors and their low molecular weight binding protein in healthy subjects and patients with growth hormone deficiency. European Journal of Clinical Investigation 20, 285292.

P Bang , K Brismar , RG Rosenfeld & K Hall (1994) Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects. Journal of Clinical Endocrinology and Metabolism 78, 960967.

GW Bates & NS Whitworth (1982) Effect of body weight reduction on plasma androgens in obese, infertile women. Fertility and Sterility 38, 406409.

RC Baxter , JM Bryson & JR Turtle (1981) The effect of fasting on liver receptors for prolactin and growth hormone. Metabolism 30, 10861090.

RC Baxter & JR Turtle (1978) Regulation of hepatic growth hormone receptors by insulin. Biochemical and Biophysical Research Communications 84, 350357.

WM Bebakar , JW Honour , D Foster , YL Liu & HS Jacobs (1990) Regulation of testicular function by insulin and transforming growth factor-beta. Steroids 55, 266270.

F Belfiore & S Iannello (1998) Insulin resistance in obesity: metabolic mechanisms and measurement methods. Molecular and Genetic Metabolism 65, 121128.

A Bereket , CH Lang , SL Blethen , J Fan , RA Frost & TA Wilson (1995 a) Insulin-like growth factor binding protein-3 proteolysis in children with insulin-dependent diabetes mellitus: a possible role for insulin in the regulation of IGFBP-3 protease activity. Journal of Clinical Endocrinology and Metabolism 80, 22822288.

A Bereket , CH Lang , SL Blethen , MC Gelato , J Fan , RA Frost & TA Wilson (1995 b) Effect of insulin on the insulin-like growth factor system in children with new-onset insulin-dependent diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 80, 13121317.

A Bereket , CH Lang & TA Wilson (1999) Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus. Hormone and Metabolism Research 31, 172181.

S Bermon , P Ferrari , P Bernard , S Altare & C Dolisi (1999) Responses of total and free insulin-like growth factor-I and insulin-like growth factor binding protein-3 after resistance exercise and training in elderly subjects. Acta Physiologia Scandinavica 165, 5156.

F Bernardi , F Petraglia , M Seppala , A Spinetti , S Bertolini , M Ferdeghini & AR Genazzani (1998) Somatotropic axis and body weight in pre-menopausal and post-menopausal women: evidence for a neuroendocrine derangement, in absence of changes of insulin-like growth factor binding protein concentrations. Human Reproduction 13, 279284.

P Bjorntorp (1992) Abdominal obesity and the metabolic syndrome. Annal of Medicine 24, 465468.

P Bjorntorp (1994) Fatty acids, hyperinsulinemia, and insulin resistance: which comes first? Current Opinion in Lipidology 5, 166174.

K Bohlke , DW Cramer , D Trichopoulos & CS Mantzoros (1998) Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology 9, 570573.

DK Bol , K Kiguchi , I Gimenez-Conti , T Rupp & J Digiovanni (1997) Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice. Oncogene 14, 17251734.

M Boni-Schnetzler , C Schmid , JL Mary , B Zimmerli , PJ Meier , J Zapf , J Schwander & ER Froesch (1990) Insulin regulates the expression of the insulin-like growth factor binding protein 2 mRNA in rat hepatocytes. Molecular Endocrinology 4, 13201326.

PF Bruning , JM Bonfrer , PA Van Noord , AA Hart , M Jong-Bakker & WJ Nooijen (1992) Insulin resistance and breast-cancer risk. International Journal of Cancer 52, 511516.

PF Bruning , J Van Doorn , JM Bonfrer , PA Van Noord , CM Korse , TC Linders & AA Hart (1995) Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. International Journal of Cancer 62, 266270.

EE Calle , TK Murphy , C Rodriguez , MJ Thun & CW Heath Jr (1998) Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control 9, 403410.

JF Cara (1994) Insulin-like growth factors, insulin-like growth factor binding proteins and ovarian androgen production. Hormone Research 42, 4954.

A Caufriez , J Golstein , P Lebrun , A Herchuelz , R Furlanetto & G Copinschi (1984) Relations between immunoreactive somatomedin C, insulin and T3 patterns during fasting in obese subjects. Clinical Endocrinology 20, 6570.

SG Chadan , RP Dill , K Vanderhoek & WS Parkhouse (1999) Influence of physical activity on plasma insulin-like growth factor-1 and insulin-like growth factor binding proteins in healthy older women. Mechanisms of Ageing and Development 109, 2134.

JM Chan , MJ Stampfer , E Giovannucci , PH Gann , J Ma , P Wilkinson , CH Hennekens & M Pollak (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279, 563566.

TC Chang , CC Tung & YL Hsiao (1994) Hormonal changes in elderly men with non-insulin-dependent diabetes mellitus and the hormonal relationships to abdominal adiposity. Gerontology 40, 260267.

IM Chapman , ML Hartman , KS Pieper , EH Skiles , SS Pezzoli , RL Hintz & MO Thorner (1998) Recovery of growth hormone release from suppression by exogenous insulin-like growth factor I (IGF-I): evidence for a suppressive action of free rather than bound IGF-I. Journal of Clinical Endocrinology and Metabolism 83, 28362842.

F Chuzel , AM Clark , O Avallet & JM Saez (1996) Transcriptional regulation of the lutropin/human choriogonadotropin receptor and three enzymes of steroidogenesis by growth factors in cultured pig Leydig cells. European Journal of Biochemistry 239, 816.

DR Clemmons , A Klibanski , LE Underwood , JW Mcarthur , EC Ridgway , IZ Beitins & JJ Van Wyk (1981) Reduction of plasma immunoreactive somatomedin C during fasting in humans. Journal of Clinical Endocrinology and Metabolism 53, 12471250.

DR Clemmons & LE Underwood (1991) Nutritional regulation of IGF-I and IGF binding proteins. Annual Review of Nutrition 11, 393412.

GA Colditz , CC Cannuscio & AL Frazier (1997) Physical activity and reduced risk of colon cancer: implications for prevention. Cancer Causes Control 8, 649667.

CA Conover & PD Lee (1990) Insulin regulation of insulin-like growth factor-binding protein production in cultured HepG2 cells. Journal of Clinical Endocrinology and Metabolism 70, 10621067.

KC Copeland , RB Colletti , JT Devlin & TL McAuliffe (1990) The relationship between insulin-like growth factor-I, adiposity, and aging. Metabolism 39, 584587.

F Cordido , FF Casanueva , JI Vidal & C Dieguez (1991) Study of insulin-like growth factor I in human obesity. Hormone Research 36, 187191.

DR Counts , H Gwirtsman , LM Carlsson , M Lesem & GB Cutler Jr (1992) The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins. Journal of Clinical Endocrinology and Metabolism 75, 762767.

JC Crave , H Lejeune , C Brebant , C Baret & M Pugeat (1995) Differential effects of insulin and insulin-like growth factor I on the production of plasma steroid-binding globulins by human hepatoblastoma-derived (Hep G2) cells. Journal of Clinical Endocrinology and Metabolism 80, 12831289.

Z Culig , A Hobisch , MV Cronauer , C Radmayr , A Hittmair , J Zhang , M Thurnher , G Bartsch & H Klocker (1996) Regulation of prostatic growth and function by peptide growth factors. Prostate 28, 392405.

E Dahlgren , LG Friberg , S Johansson , B Lindstrom , A Oden , G Samsioe & PO Janson (1991) Endometrial carcinoma; ovarian dysfunction – a risk factor in young women. European Journal of Obstetrics, Gynecology and Reproductive Biology 41, 143150.

RA DeFronzo (1988) Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37, 667687.

ME Del Giudice , IG Fantus , S Ezzat , G McKeown-Eyssen , D Page & PJ Goodwin (1998) Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Research and Treatment 47, 111120.

MD DeMoura , D Choi , EY Adashi & DW Payne (1997) Insulin-like growth factor-I-mediated amplification of follicle-stimulating hormone-supported progesterone accumulation by cultured rat granulosa cells: enhancement of steroidogenic enzyme activity and expression. Biology of Reproduction 56, 946953.

RB Dickson & ME Lippman (1995) Growth factors in breast cancer. Endocrinology Review 16, 559589.

J DiGiovanni , K Kiguchi , A Frijhoff , E Wilker , DK Bol , L Beltran , S Moats , A Ramirez , J Jorcano & C Conti (2000 b) Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proceedings of the National Academy of Sciences USA 97, 34553460.

L Di Luigi , FG Conti , A Casini , L Guidetti , G Zezze , F Pigozzi , G Spera , G Fortunio & F Romanelli (1997) Growth hormone and insulin-like growth factor I responses to moderate submaximal acute physical exercise in man: effects of octreotide, a somatostatin analogue, administration. International Journal of Sports Medicine 18, 257263.

A Dunaif (1999) Insulin action in the polycystic ovary syndrome. Endocrinology and Metabolism Clinics of North America 28, 341359.

DB Dunger & TD Cheetham (1996) Growth hormone insulin-like growth factor I axis in insulin-dependent diabetes mellitus. Hormone Research 46, 26.

NE Eaton , GK Reeves , PN Appleby & TJ Key (1999) Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies. British Journal of Cancer 80, 930934.

DA Ehrmann (1999) Insulin-lowering therapeutic modalities for polycystic ovary syndrome. Endocrinology and Metabolism Clinics of North America 28, 423438.

AN Elias , MR Pandian , L Wang , E Suarez , N James & AF Wilson (2000) Leptin and IGF-I levels in unconditioned male volunteers after short-term exercise. Psychoneuroendocrinology 25, 453461.

EM Erfurth , LE Hagmar , M Saaf & K Hall (1996) Serum levels of insulin-like growth factor I and insulin-like growth factor-binding protein 1 correlate with serum free testosterone and sex hormone binding globulin levels in healthy young and middle-aged men. Clinical Endocrinology 44, 659664.

J Everhart & D Wright (1995) Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. Journal of the American Medical Association 273, 16051609.

B Falkner , K Sherif , A Sumner & H Kushner (1999) Hyperinsulinism and sex hormones in young adult African Americans. Metabolism 48, 107112.

RL Ferrini & E Barrett-Connor (1998) Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. American Journal of Epidemiology 147, 750754.

LT Frame , RW Hart & JE Leakey (1998) Caloric restriction as a mechanism mediating resistance to environmental disease. Environmental Health Perspective 106, Suppl. 1, 313324.

GD Friedman & SK Van Den Eeden (1993) Risk factors for pancreatic cancer: an exploratory study. International Journal of Epidemiology 22, 3037.

J Frystyk , E Vestbo , C Skjaerbaek , CE Mogensen & H Orskov (1995) Free insulin-like growth factors in human obesity. Metabolism 44, 3744.

R Gama , JD Teale & V Marks (1990) The effect of synthetic very low calorie diets on the GH-IGF-1 axis in obese subjects. Clinical Chimica Acta 188, 3138.

MD Gammon , EM John & JA Britton (1998) Recreational and occupational physical activities and risk of breast cancer. Journal of the National Cancer Institute 90, 100117.

SM Gapstur , PH Gann , W Lowe , K Liu , L Colangelo & A Dyer (2000) Abnormal glucose metabolism and pancreatic cancer mortality. Journal of the American Medical Association 283, 25522558.

A Giacosa , S Franceschi , C La Vecchia , A Favero & R Andreatta (1999) Energy intake, overweight, physical exercise and colorectal cancer risk. European Journal of Cancer Prevention 8, Suppl. 1, S53S60.

ZP Gill , CM Perks , PV Newcomb & JM Holly (1997) Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. Journal of Biological Chemistry 272, 2560225607.

E Giovannucci (1995) Insulin and colon cancer. Cancer Causes Control 6, 164179.

E Giovannucci , EB Rimm , MJ Stampfer , GA Colditz & WC Willett (1998) Diabetes mellitus and risk of prostate cancer. Cancer Causes Control 9, 39.

A Giustina & WB Wehrenberg (1995) Influence of thyroid hormones on the regulation of growth hormone secretion. European Journal of Endocrinology 133, 646653.

NH Golden , P Kreitzer , MS Jacobson , FI Chasalow , J Schebendach , SM Freedman & IR Shenker (1994) Disturbances in growth hormone secretion and action in adolescents with anorexia nervosa. Journal of Pediatrics 125, 655660.

JJ Grimm (1999) Interaction of physical activity and diet: implications for insulin-glucose dynamics. Public Health Nutrition 2, 363368.

PB Grino , JE Griffin & JD Wilson (1990) Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone. Endocrinology 126, 11651172.

SM Haffner , P Karhapaa , L Mykkanen & M Laakso (1994) Insulin resistance, body fat distribution, and sex hormones in men. Diabetes 43, 212219.

SM Haffner , L Mykkanen , RA Valdez & MS Katz (1993 a) Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. Journal of Clinical Endocrinology and Metabolism 77, 16101615.

SE Hankinson , WC Willett , GA Colditz , DJ Hunter , DS Michaud , B Deroo , B Rosner , FE Speizer & M Pollak (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351, 13931396.

HA Hill & H Austin (1996) Nutrition and endometrial cancer. Cancer Causes Control 7, 1932.

KK Ho , AJ O'Sullivan , AJ Weissberger & JJ Kelly (1996) Sex steroid regulation of growth hormone secretion and action. Hormone Research 45, 6773.

Z Hochberg , P Hertz , V Colin , S Ish-Shalom , D Yeshurun , MB Youdim & T Amit (1992) The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa. Metabolism 41, 106112.

NJ Hopkins , PM Jakeman , SC Hughes & JM Holly (1994) Changes in circulating insulin-like growth factor-binding protein-1 (IGFBP-1) during prolonged exercise: effect of carbohydrate feeding. Journal of Clinical Endocrinology and Metabolism 79, 18871890.

FB Hu , JE Manson , S Liu , D Hunter , GA Colditz , KB Michels , FE Speizer & E Giovannucci (1999) Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. Journal of The National Cancer Institute 91, 542547.

H Jasper , P Pennis , M Vitale , A Mella , G Ropelato & A Chervin (1999) Evaluation of disease activity by IGF-I and IGF binding protein-3 (IGFBP3) in acromegaly patients distributed according to a clinical score. Journal of Endocrinological Investigation 22, 2934.

BT Ji , MC Hatch , WH Chow , JK McLaughlin , Q Dai , GR Howe , YT Gao & JF Fraumeni Jr (1996) Anthropometric and reproductive factors and the risk of pancreatic cancer: a case-control study in Shanghai, China. International Journal of Cancer 66, 432437.

JI Jones & DR Clemmons (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocrine Reviews 16, 334.

A Juul , A Flyvbjerg , J Frystyk , J Muller & NE Skakkebaek (1996) Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty. Clinical Endocrinology 44, 515523.

A Juul , K Main , WF Blum , J Lindholm , MB Ranke & NE Skakkebaek (1994) The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients. Clinical Endocrinology 41, 8593.

R Kaaks (1996) Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control 7, 605625.

R Kaaks , P Toniolo , A Akhmedkhanov , A Lukanova , C Biessy , H Dechaud , S Rinaldi , A Zeleniuch-Jacquotte , RE Shore & E Riboli (2000) Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins and colorectal cancer risk in women. Journal of the National Cancer Institute 92, 15921600.

M Karas , M Danilenko , D Fishman , D LeRoith , J Levy & Y Sharon (1997) Membrane-associated insulin-like growth factor-binding protein-3 inhibits insulin-like growth factor-I-induced insulin-like growth factor-I receptor signaling in ishikawa endometrial cancer cells. Journal of Biological Chemistry 272, 1651416520.

TJ Key , NE Allen , PK Verkasalo & E Banks (2001) Energy balance and cancer: the role of sex hormones. Proceedings of the Nutrition Society 60, 8189.

TJ Key & MC Pike (1988 a) The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. British Journal of Cancer 57, 205212.

TJ Key & MC Pike (1988 b) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. European Journal of Cancer and Clinical Oncology 24, 2943.

DS Kiddy , D Hamilton-Fairley , M Seppälä , R Koistinen , VH James , MJ Reed & S Franks (1989) Diet-induced changes in sex hormone binding globulin and free testosterone in women with normal or polycystic ovaries: correlation with serum insulin and insulin-like growth factor-I. Clinical Endocrinology 31, 757763.

VA Koivisto , H Yki-Jarvinen & RA DeFronzo (1986) Physical training and insulin sensitivity. Diabetes and Metabolism Reviews 1, 445481.

LN Kolonel (1996) Nutrition and prostate cancer. Cancer Causes Control 7, 83–44.

PG Kopelman , N White , TR Pilkington & SL Jeffcoates (1981) The effect of weight loss on sex steroid secretion and binding in massively obese women. Clinical Endocrinology 15, 113116.

SB Kristiansen , A Endoh , PR Casson , JE Buster & PJ Hornsby (1997) Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells. Steroids 62, 258265.

D Kritchevsky (1999) Caloric restriction and experimental carcinogenesis. Toxicological Sciences 52, 1316.

C La Vecchia , E Negri , S Franceschi , B D'Avanzo & P Boyle (1994) A case-control study of diabetes mellitus and cancer risk. British Journal of Cancer 70, 950953.

AV Lee , SG Hilsenbeck & D Yee (1998) IGF system components as prognostic markers in breast cancer. Breast Cancer Research and Treatment 47, 295302.

PD Lee , LC Giudice , CA Conover & DR Powell (1997) Insulin-like growth factor binding protein-1: recent findings and new directions. Proceedings of the Society for Experimental Biology and Medicine 216, 319357.

T Lin , J Haskell , N Vinson & L Terraccio (1986) Direct stimulatory effects of insulin-like growth factor-I on Leydig cell steroidogenesis in primary culture. Biochemical and Biophysical Research Communications 137, 950956.

PE Lonning , DC Johannessen , EA Lien , D Ekse , T Fotsis & H Adlercreutz (1995) Influence of tamoxifen on sex hormones, gonadotrophins and sex hormone binding globulin in postmenopausal breast cancer patients. Journal of Steroid Biochemistry and Molecular Biology 52, 491496.

A McTiernan , C Ulrich , S Slates & J Potter (1998) Physical activity and cancer etiology: associations and mechanisms. Cancer Causes Control 9, 487509.

J Ma , MN Pollak , E Giovannucci , JM Chan , Y Tao , CH Hennekens & MJ Stampfer (1999) Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. Journal of the National Cancer Institute 91, 620625.

M Maes , JM Ketelslegers & LE Underwood (1983) Low plasma somatomedin-C in streptozotocin-induced diabetes mellitus. Correlation with changes in somatogenic and lactogenic liver binding sites. Diabetes 32, 10601069.

DA Magoffin , KM Kurtz & GF Erickson (1990) Insulin-like growth factor-I selectively stimulates cholesterol side-chain cleavage expression in ovarian theca-interstitial cells. Molecular Endocrinology 4, 489496.

DA Magoffin & SR Weitsman (1993 a) Differentiation of ovarian theca-interstitial cells in vitro: regulation of 17 alpha-hydroxylase messenger ribonucleic acid expression by luteinizing hormone and insulin-like growth factor-I. Endocrinology 132, 19451951.

DA Magoffin & SR Weitsman (1993 b) Insulin-like growth factor-I stimulates the expression of 3 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid in ovarian theca-interstitial cells. Biology of Reproduction 48, 11661173.

O Manousos , J Souglakos , C Bosetti , A Tzonou , V Chatzidakis , D Trichopoulos , HO Adami & C Mantzoros (1999) IGF-I and IGF-II in relation to colorectal cancer. International Journal of Cancer 83, 1517.

CS Mantzoros , A Tzonou , LB Signorello , M Stampfer , D Trichopoulos & HO Adami (1997) Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. British Journal of Cancer 76, 11151118.

TJ Merimee , J Zapf & ER Froesch (1982) Insulin-like growth factors in the fed and fasted states. Journal of Clinical Endocrinology and Metabolism 55, 9991002.

S Mesiano , SL Katz , JY Lee & RB Jaffe (1997) Insulin-like growth factors augment steroid production and expression of steroidogenic enzymes in human fetal adrenal cortical cells: implications for adrenal androgen regulation. Journal of Clinical Endocrinology and Metabolism 82, 13901396.

MA Moore , CB Park & H Tsuda (1998) Physical exercise: a pillar for cancer prevention? European Journal of Cancer Prevention 7, 177193.

AJ Morales , GA Laughlin , T Butzow , H Maheshwari , G Baumann & SS Yen (1996) Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. Journal of Clinical Endocrinology and Metabolism 81, 28542864.

M Moseson , KL Koenig , RE Shore & BS Pasternack (1993) The influence of medical conditions associated with hormones on the risk of breast cancer. International Journal of Epidemiology 22, 10001009.

SY Nam , EJ Lee , KR Kim , BS Cha , YD Song , SK Lim , HC Lee & KB Huh (1997) 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. International Journal of Obesity Related Metabolism Disorder 21, 355359.

BJ Nicklas , AJ Ryan , MM Treuth , SM Harman , MR Blackman , BF Hurley & MA Rogers (1995) Testosterone, growth hormone and IGF-I responses to acute and chronic resistive exercise in men aged 55–70 years. International Journal of Sports and Medicine 16, 445450.

BL Nyomba , L Berard & LJ Murphy (1997) Free insulin-like growth factor I (IGF-I) in healthy subjects: relationship with IGF-binding proteins and insulin sensitivity. Journal of Clinical Endocrinology and Metabolism 82, 21772181.

BA O'Mara , T Byers & E Schoenfeld (1985) Diabetes mellitus and cancer risk: a multisite case-control study. Journal of Chronic Disease 38, 435441.

F Parazzini , C LaVecchia , E Negri , GL Riboldi , M Surace , G Benzi , A Main & F Chiaffarino (1999) Diabetes and endometrial cancer: an Italian case-control study. International Journal of Cancer 81, 539542.

R Pasquali , F Casimirri , S Cantobelli , N Melchionda , AM Morselli Labate , R Fabbri , M Capelli & L Bortoluzzi (1991) Effect of obesity and body fat distribution on sex hormones and insulin in men. Metabolism 40, 101104.

R Pasquali , F Casimirri & V Vicennati (1997) Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome. Human Reproduction 12, Suppl. 1, 8287.

A Penhoat , R Ouali , I Viard , D Langlois & JM Saez (1996) Regulation of primary response and specific genes in adrenal cells by peptide hormones and growth factors. Steroids 61, 176183.

E Petridou , Y Papadiamantis , C Markopoulos , E Spanos , N Dessypris & D Trichopoulos (2000) Leptin and insulin growth factor I in relation to breast cancer (Greece). Cancer Causes Control 11, 383388.

J Pfeilschifter , C Scheidt-Nave , G Leidig-Bruckner , HW Woitge , WF Blum , C Wuster , D Haack & R Ziegler (1996) Relationship between circulating insulin-like growth factor components and sex hormones in a population-based sample of 50- to 80-year-old men and women. Journal of Clinical Endocrinology and Metabolism 81, 25342540.

SR Plymate , RE Jones , LA Matej & KE Friedl (1988) Regulation of sex hormone binding globulin (SHBG) production in Hep G2 cells by insulin. Steroids 52, 339340.

L Poretsky , NA Cataldo , Z Rosenwaks & LC Giudice (1999) The insulin-related ovarian regulatory system in health and disease. Endocrine Reviews 20, 535582.

MC Postel-Vinay , E Cohen-Tanugi & J Charrier (1982) Growth hormone receptors in rat liver membranes: effects of fasting and refeeding, and correlation with plasma somatomedin activity. Molecular and Cellular Endocrinology 28, 657669.

D Prager , HL Li , S Asa & S Melmed (1994) Dominant negative inhibition of tumorigenesis in vivo by human insulin-like growth factor I receptor mutant. Proceedings of the National Academy of Sciences USA 91, 21812185.

M Pugeat , JC Crave , M Elmidani , MH Nicolas , M Garoscio-Cholet , H Lejeune , H Dechaud & J Tourniaire (1991) Pathophysiology of sex hormone binding globulin (SHBG): relation to insulin. Journal of Steroid Biochemistry and Molecular Biology 40, 841849.

M Pugeat & PH Ducluzeau (1999) Insulin resistance, polycystic ovary syndrome and metformin. Drugs 58, Suppl. 1, 4146.

M Ragozzino , LJ Melton III, CP Chu & PJ Palumbo (1982) Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. Journal of Chronic Disease 35, 1319.

R Rajah , B Valentinis & P Cohen (1997) Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta 1 on programmed cell death through a p53- and IGF-independent mechanism. Journal of Biological Chemistry 272, 1218112188.

PJ Randle (1998) Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes and Metabolism Reviews 14, 263283.

MH Rasmussen , J Frystyk , T Andersen , L Breum , JS Christiansen & J Hilsted (1994) The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone. Metabolism 43, 315319.

MH Rasmussen , A Hvidberg , A Juul , KM Main , A Gotfredsen , NE Skakkebaek , J Hilsted & NE Skakkebaek (1995 a) Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. Journal of Clinical Endocrinology and Metabolism 80, 14071415.

MH Rasmussen , A Juul , LL Kjems , NE Skakkebaek & J Hilsted (1995 b) Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity. Journal of Clinical Endocrinology and Metabolism 80, 796801.

MM Rechler (1997) Growth inhibition by insulin-like growth factor (IGF) binding protein-3 – what's IGF got to do with it? Endocrinology 138, 26452647.

CA Roelen , WR DeVries , HP Koppeschaar , C Vervoorn , JH Thijssen & MA Blankenstein (1997) Plasma insulin-like growth factor-I and high affinity growth hormone-binding protein levels increase after two weeks of strenuous physical training. International Journal of Sports and Medicine 18, 238241.

RK Ross , A Paganini-Hill , PC Wan & MC Pike (2000) Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. Journal of the National Cancer Institute 92, 328332.

EM Rutanen (1998) Insulin-like growth factors in endometrial function. Gynecological Endocrinology 12, 399406.

EM Rutanen , T Nyman , P Lehtovirta , M Ammala & F Pekonen (1994) Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the endometrium: a molecular mechanism associating endometrial cancer with its risk factors. International Journal of Cancer 59, 307312.

C Schairer , J Lubin , R Troisi , S Sturgeon , L Brinton & R Hoover (2000) Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. Journal of the American Medical Association 283, 485491.

TP Scheett , PJ Mills , MG Ziegler , J Stoppani & DM Cooper (1999) Effect of exercise on cytokines and growth mediators in prepubertal children. Pediatric Research 46, 429434.

RE Schoen , CM Tangen , LH Kuller , GL Burke , M Cushman , RP Tracy , A Dobs & PJ Savage (1999) Increased blood glucose and insulin, body size, and incident colorectal cancer. Journal of the National Cancer Institute 91, 11471154.

AJ Schwarz , JA Brasel , RL Hintz , S Mohan & DM Cooper (1996) Acute effect of brief low- and high-intensity exercise on circulating insulin-like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men. Journal of Clinical Endocrinology and Metabolism 81, 34923497.

JC Seidell , P Björntorp , L Sjoström , H Kvist & R Sannerstedt (1990) Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism 39, 897901.

TA Sellers , KE Anderson , JE Olson & AR Folsom (1998) Family histories of diabetes mellitus and breast cancer and incidence of postmenopausal breast cancer. Epidemiology 9, 102105.

SM Shoff & PA Newcomb (1998) Diabetes, body size, and risk of endometrial cancer. American Journal of Epidemiology 148, 234240.

XO Shu , LA Brinton , W Zheng , YT Gao , J Fan & JF Fraumeni Jr (1991) A population-based case-control study of endometrial cancer in Shanghai, China. International Journal of Cancer 49, 3843.

DT Silverman , M Schiffman , J Everhart , A Goldstein , KD Lillemoe , GM Swanson , AG Schwartz , LM Brown , RS Greenberg , JB Schoenberg , LM Pottern , RN Hoover & JF Fraumeni (1999) Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. British Journal of Cancer 80, 18301837.

DT Silverman , CA Swanson , G Gridley , S Wacholder , RS Greenberg , LM Brown , RB Hayes , GM Swanson , JB Schoenberg , LM Pottern , AG Schwartz , JF Fraumeni Jr & RN Hoover (1998) Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. Journal of the National Cancer Institute 90, 17101719.

A Singh , D Hamilton-Fairley , R Koistnen , M Seppälä , VH James , S Franks & MJ Reed (1990) Effect of insulin-like growth factor-type I (IGF-I) and insulin on the secretion of sex hormone binding globulin and IGF-I binding protein (IBP-I) by human hepatoma cells. Journal of Endocrinology 124, R1R3.

P Singh & N Rubin (1993) Insulinlike growth factors and binding proteins in colon cancer. Gastroenterology 105, 12181237.

P Stattin , A Bylund , S Rinaldi , C Biessy , H Dechaud , U-H Stenman , L Egevad , E Riboli , G Hallmans & R Kaaks (2000) Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. Journal of the National Cancer Institute 92 (In the Press).

P Stein , LE Bussmann & M Tesone (1995) In vivo regulation of the steroidogenic activity of rat luteal cells by insulin. Journal of Steroid Biochemistry and Molecular Biology 52, 329335.

DS Straus & CD Takemoto (1990) Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Molecular Endocrinology 4, 91100.

AM Suikkari , VA Koivisto , EM Rutanen , H Yki-Jarvinen , SI Karonen & M Seppälä (1988) Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. Journal of Clinical Endocrinology and Metabolism 66, 266272.

T Tanaka , H Maesaka & S Suwa (1985) Changes in somatomedin activity in anorexia nervosa. Endocrinologica Japonica 32, 891897.

GS Tannenbaum , HJ Guyda & BI Posner (1983) Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain. Science 220, 7779.

JP Thissen , JM Ketelslegers & IE Underwood (1994) Nutritional regulation of the insulin-like growth factors. Endocrine Reviews 15, 80101.

HV Thomas , GK Reeves & TJ Key (1997) Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8, 922928.

G Tibblin , A Adlerberth , G Lindstedt & P Bjorntorp (1996) The pituitary-gonadal axis and health in elderly men: a study of men born in 1913. Diabetes 45, 16051609.

P Tollet , B Enberg & A Mode (1990) Growth hormone (GH) regulation of cytochrome P-450IIC12, insulin-like growth factor-I (IGF-I), and GH receptor messenger RNA expression in primary rat hepatocytes: a hormonal interplay with insulin, IGF-I, and thyroid hormone. Molecular Endocrinology 4, 19341942.

P Toniolo , PF Bruning , A Akhmedkhanov , JMG Bonfrer , KL Koenig , A Lukanova , RE Shore & AZ Jacquotte (2000) Serum insulin-like growth factor-I and breast cancer. International Journal of Cancer (In the Press).

R Troisi , N Potischman , RN Hoover , P Siiteri & LA Brinton (1997) Insulin and endometrial cancer. American Journal of Epidemiology 146, 476482.

SM Twigg & RC Baxter (1998) Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. Journal of Biological Chemistry 273, 60746079.

TG Unterman (1993) Insulin-like growth factor binding protein-1: identification, purification, and regulation in fetal and adult life. Advances in Experimental Medicine and Biology 343, 215226.

RJ Urban , JC Garmey , MA Shupnik & JD Veldhuis (1990) Insulin-like growth factor type I increases concentrations of messenger ribonucleic acid encoding cytochrome P450 cholesterol side-chain cleavage enzyme in primary cultures of porcine granulosa cells. Endocrinology 127, 24812488.

G Ursin , MP Longnecker , RW Haile & S Greenland (1995) A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology 6, 137141.

ML Vance , ML Hartman & MO Thorner (1992) Growth hormone and nutrition. Hormone Research 38, Suppl. 1, 8588.

JD Veldhuis , AY Liem , S South , A Weltman , J Weltman , DA Clemmons , R Abbott , T Mulligan , ML Johnson & S Pincus (1995) Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay. Journal of Clinical Endocrinology and Metabolism 80, 32093222.

A Vermeulen (1996) Decreased androgen levels and obesity in men. Annals of Medicine 28, 1315.

A Vermeulen , JM Kaufman & VA Giagulli (1996) Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. Journal of Clinical Endocrinology and Metabolism 81, 18211826.

JD Wallace , RC Cuneo , R Baxter , H Orskov , N Keay , C Pentecost , R Dall , T Rosen , JO Jorgensen , A Cittadini , S Longobardi , L Sacca , JS Christiansen , BA Bengtsson , & PH Sonksen (1999) Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult makes: a potential test for GH abuse in sport. Journal of Clinical Endocrinology and Metabolism 84, 35913601.

WB Wehrenberg & A Giustina (1992) Basic counterpoint: mechanisms and pathways of gonadal steroid modulation of growth hormone secretion. Endocrine Reviews 13, 299308.

E Weiderpass , G Gridley , I Persson , O Nyren , A Ekbom & HO Adam (1997) Risk of endometrial and breast cancer in patients with diabetes mellitus. International Journal of Cancer 71, 360363.

E Weiderpass , T Partanen , R Kaaks , H Vainio , M Porta , T Kauppinen , A Ojajarvi , P Boffetta & N Malats (1998) Occurrence, trends and environment etiology of pancreatic cancer. Scandinavian Journal of Work and Environmental Health 24, 165174.

E Weiderpass , I Persson , HO Adami , C Magnusson , A Lindgren & JA Baron (2000) Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer. Cancer Causes Control 11, 185192.

R Weindruch (1992) Effect of caloric restriction on age-associated cancers. Experimental Gerontology 27, 575581.

HA Weiss , LA Brinton , NA Potischman , D Brogan , RJ Coates , MD Gammon , KE Malone & JB Schoenberg (1999) Breast cancer risk in young women and history of selected medical conditions. International Journal of Epidemiology 28, 816823.

H Werner & D LeRoith (1996) The role of the insulin-like growth factor system in human cancer. Advances in Cancer Research 68, 183223.

L Wideroff , G Gridley , L Mellemkjaer , WH Chow , M Linet , S Keehn , K Borch-Johnsen & JH Olsen (1997) Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. Journal of the National Cancer Institute 89, 13601365.

E Wilker , D Bol , K Kiguchi , T Rupp , L Beltran & J DiGiovanni (1999) Enhancement of susceptibility to diverse skin tumor promoters by activation of the insulin-like growth factor-1 receptor in the epidermis of transgenic mice. Molecular Carcinogenesis 25, 122131.

JC Will , DA Galuska , F Vinicor & EE Calle (1998) Colorectal cancer: another complication of diabetes mellitus? American Journal of Epidemiology 147, 816825.

JC Will , F Vinicor & EE Calle (1999) Is diabetes mellitus associated with prostate cancer incidence and survival? Epidemiology 10, 313318.

A Wolk , CS Mantzoros , SO Andersson , R Bergstrom , LB Signorello , P Lagiou , HO Adami & D Trichopoulos (1998) Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. Journal of the National Cancer Institute 90, 911915.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: