[en] Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Rinaldi, Sabina
Cleveland, Rebecca
Norat, Teresa
Biessy, Carine
Rohrmann, Sabine
Linseisen, Jakob
Boeing, Heiner
Pischon, Tobias
Panico, Salvatore
Agnoli, Claudia
Palli, Domenico
Tumino, Rosario
Vineis, Paolo
Peeters, Petra H. M.
van Gils, Carla H.
Bueno-de-Mesquita, Bas H.
Vrieling, Alina
Allen, Naomi E.
Roddam, Andrew
Bingham, Sheila
Khaw, Kay-Tee
Manjer, Jonas
Borgquist, Signe
Dumeaux, Vanessa
Torhild Gram, Inger
Lund, Eiliv
Trichopoulou, Antonia
Makrygiannis, Georgios ; Université de Liège - ULiège > Département des sciences cliniques > Chirurgie cardio-vasculaire et thoracique
Thissen JP, Ketelslegers JM, Underwood LE. Nutritional regulation of the insulinlike growth factors. Endocr Rev 1994;15: 80-101.
Estivariz CF, Ziegler TR. Nutrition and the insulin-like growth factor system. Endocrine 1997;7:65-71.
Yu H, Berkel H. Insulin-like growth factors and cancer. J LA State Med Soc 1999;151: 218-23.
Kaaks R, Lukanova A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc 2001;60: 91-106.
LeRoith D, Roberts CT, Jr. The insulin-like growth factor system and cancer. Cancer Lett 2003;195:127-37.
Harrela M, Koistinen H, Kaprio J, Lehtovirta M, Tuomilehto J, Eriksson J, Toivanen L, Koskenvuo M, Leinonen P, Koistinen R, Seppala M. Genetic and environmental components of interindividual variation in circulating levels of IGF-I. IGF-II, IGFBP-1, and. IGFBP-3. J Clin Invest 1996;98:2612-15.
Kao PC, Matheny AP, Jr., Lang CA. Insulin-like growth factor-I comparisons in healthy twin children. J. Clin. Endocrinol. Metab. 1994;78(2):310-2.
Juul A, Main K, Blum WF, Lindholm J, Ranke MB, Skakkebaek NE. 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. Clin. Endocrinol (Oxf). 1994;41(1):85-93.
Norat T, Dossus L, Rinaldi S, Overvad K, Gronbaek H, Tjonneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault MC, Boeing H, Lahmann PH, Linseisen J, et al. Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women. Eur J Clin Nutr 2007;61:91-8.
Holmes MD, Pollak MN, Willett WC, Hankinson SE. Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol Biomarkers Prev 2002;11:852-61.
Norat T, Bingham S, Ferrari P, Slimani N, Jenab M, Mazuir M, Overvad K, Olsen A, Tjonneland A, Clavel F, Boutron-Ruault MC, Kesse E, et al. Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition. J Natl Cancer Inst 2005;97: 906-16.
DeLellis K, Rinaldi S, Kaaks RJ, Kolonel LN, Henderson B, Le ML. Dietary and lifestyle correlates of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3): the multiethnic cohort. Cancer Epidemiol Biomarkers Prev. 2004;13:1444-51.
Lukanova A, Toniolo P, Akhmedkhanov A, Hunt K, Rinaldi S, Zeleniuch-Jacquotte A, Haley NJ, Riboli E, Stattin P, Lundin E, Kaaks R. A cross-sectional study of IGF-I determinants in women. Eur J Cancer Prev 2001;10:443-52.
Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer 2004;4: 505-18.
Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 2000;21: 215-44.
De Meyts P, Whittaker J. Structural biology of insulin and IGF1 receptors: implications for drug design. Nat Rev Drug Discov 2002;1:769-83.
Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 2007;28:20-47.
Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulinlike growth factor (IGF)-I. IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004;363:1346-53.
Voskuil DW, Vrieling A, van't Veer LJ, Kampman E, Rookus MA. The insulin-like growth factor system in cancer prevention: potential of dietary intervention strategies. Cancer. Epidemiol. Biomarkers. Prev. 2005; 14(1):195-203.
Vrieling A, Rookus MA, Kampman E, Bonfrer JM, Korse CM, van DJ, Lampe JW, Cats A, Witteman BJ, van Leeuwen FE, van't Veer LJ, Voskuil DW. Isolated isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk. J Nutr 2007;137:379-83.
Vrieling A, Rookus MA, Kampman E, Bonfrer JM, Bosma A, Cats A, van DJ, Korse CM, Witteman BJ, van Leeuwen FE, van't Veer LJ, Voskuil DW. No effect of red clover-derived isoflavone intervention on the insulin-like growth factor system in women at increased risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 2008;17:2585-93.
Kaaks R, Bellati C, Venturelli E, Rinaldi S, Secreto G, Biessy C, Pala V, Sieri S, Berrino F. Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the Diet and Androgens (DIANA) Randomised Trial. Eur J Clin Nutr 2003;57:1079-88.
Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 2008;7:681-7.
Hassan AB, Macaulay VM. The insulin-like growth factor system as a therapeutic target in colorectal cancer. Ann Oncol 2002;13:349-56.
Yee D. Targeting insulin-like growth factor pathways. Br J Cancer 2006;94:465-8.
Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, Stampfer MJ. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 1999;91: 620-5.
Giovannucci E, Pollak MN, Platz EA, Willett WC, Stampfer MJ, Majeed N, Colditz GA, Speizer FE, Hankinson SE. A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomarkers Prev 2000;9:345-9.
Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E. Serum C-peptide, insulin-like growth factor (IGF)-I. IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 2000;92:1592-600.
Probst-Hensch NM, Yuan JM, Stanczyk FZ, Gao YT, Ross RK, Yu MC. IGF-1. IGF-2 and. IGFBP-3 in prediagnostic serum: association with colorectal cancer in a cohort of Chinese men in Shanghai. Br J Cancer 2001;85:1695-9.
Palmqvist R, Hallmans G, Rinaldi S, Biessy C, Stenling R, Riboli E, Kaaks R. Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden. Gut 2002;50:642-6.
Nomura AM, Stemmermann GN, Lee J, Pollak MN. Serum insulin-like growth factor I and subsequent risk of colorectal cancer among Japanese-American men. Am J Epidemiol 2003;158:424-31.
Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE, Giovannucci E. A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 2005;14:850-5.
Otani T, Iwasaki M, Sasazuki S, Inoue M, Tsugane S. Plasma C-peptide, insulin-like growth factor-I, insulin-like growth factor binding proteins and risk of colorectal cancer in a nested case-control study: the Japan public health center-based prospective study. Int J Cancer 2007;120: 2007-12.
Kaaks R, Rinaldi S, Lukanova A, Akhmedkhanov A, Zeleniuch-Jacquotte A, Toniolo P. Correspondence re: Giovannucci et al. A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomark Prev 2000;9:345-9. Cancer Epidemiol Biomarkers Prev 2001;10:1103-4.
Rinaldi S, Kaaks R, Zeleniuch-Jacquotte A, Arslan AA, Shore RE, Koenig KL, Dossus L, Riboli E, Stattin P, Lukanova A, Toniolo P. Insulin-like growth factor-I. IGF binding protein-3, and breast cancer in young women: a comparison of risk estimates using different peptide assays. Cancer Epidemiol Biomarkers Prev 2005;14:48-52.
Bingham S, Riboli E. Diet and cancer - the European Prospective Investigation into Cancer and Nutrition. Nat Rev Cancer 2004;4:206-15.
Gram IT, Norat T, Rinaldi S, Dossus L, Lukanova A, Tehard B, Clavel-Chapelon F, van Gils CH, van Noord PA, Peeters PH, Bueno-de-Mesquita HB, Nagel G, et al. Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women. Int J Obes (Lond) 2006;30:1623-31.
Allen NE, Appleby PN, Davey GK, Key TJ, Rinaldi S, Kaaks R. The effect of diet on serum insulin-like growth-factor-I and its main binding proteins. IARC Sci Publ 2002;156:295-6.
Giovannucci E, Pollak M, Liu Y, Platz EA, Majeed N, Rimm EB, Willett WC. Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men. Cancer. Epidemiol. Biomarkers. Prev. 2003;12(2):84-9.
Pischon T, Lahmann PH, Boeing H, Friedenreich C, Norat T, Tjonneland A, Halkjaer J, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Guernec G, Bergmann MM, et al. Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2006; 98:920-31.
Cho E, Smith-Warner SA, Spiegelman D, Beeson WL, van den Brandt PA, Colditz GA, Folsom AR, Fraser GE, Freudenheim JL, Giovannucci E, Goldbohm RA, Graham S, et al. Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies. J Natl Cancer Inst 2004;96:1015-22.
Kesse E, Boutron-Ruault MC, Norat T, Riboli E, Clavel-Chapelon F. Dietary calcium, phosphorus, vitamin D, dairy products and the risk of colorectal adenoma and cancer among French women of the E3N-EPIC prospective study. Int J Cancer 2005;117:137-44.
Bingham SA, Day NE, Luben R, Ferrari P, Slimani N, Norat T, Clavel-Chapelon F, Kesse E, Nieters A, Boeing H, Tjonneland A, Overvad K, et al. Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study. Lancet 2003;361: 1496-501.
Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr 2003;78(3 Suppl):559S-69S.
Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M, Charrondiere UR, Hemon B, Casagrande C, Vignat J, Overvad K, Tjonneland A, et al. European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 2002; 5(6B):1113-24.
Kaaks R, Berrino F, Key T, Rinaldi S, Dossus L, Biessy C, Secreto G, Amiano P, Bingham S, Boeing H, Bueno de Mesquita HB, Chang-Claude J, et al. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2005; 97:755-65.
Jane Ellis M, Livesey JH, Evans MJ. Hormone stability in human whole blood. Clin Biochem 2003;36:109-12.
Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 1992;135:301-9.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.
Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, Howard BV, Wylie-Rosett J, Anderson GL, Ho GY, Kaplan RC, Li J, et al. Insulin, insulin-like growth factor-I, endogenous estradiol, and risk of colorectal cancer in postmenopausal women. Cancer Res 2008;68:329-37.
Max JB, Limburg PJ, Ogunseitan A, Stolzenberg-Solomon RZ, Vierkant RA, Pollak MJ, Sellers TA, Virtamo J, Cerhan JR, Albanes D. IGF-I. IGFBP-3, and IGF-I/IGFBP-3 ratio: no. association with incident colorectal cancer in the alphatocopherol beta-carotene. Cancer Epidemiol Biomarkers Prev 2008;17:1832-4.
Lukanova A, Zeleniuch-Jacquotte A, Lundin E, Micheli A, Arslan AA, Rinaldi S, Muti P, Lenner P, Koenig KL, Biessy C, Krogh V, Riboli E, et al. Prediagnostic levels of C-peptide. IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer. Int J Cancer 2004;108:262-8.
Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, Metter EJ, Chen C, Weiss NS, Fitzpatrick A, Hsing AW, Lacey JV, Jr. et al. Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med 2008;149:461-8.
Teramukai S, Rohan T, Lee KY, Eguchi H, Oda T, Kono S. Insulin-like growth factor (IGF)-I. IGF-binding protein-3 and colorectal adenomas in Japanese men. Jpn J Cancer Res 2002;93:1187-94.
Ma J, Giovannucci E, Pollak M, Chan JM, Gaziano JM, Willett W, Stampfer MJ. Milk intake, circulating levels of insulin-like growth factor-I, and risk of colorectal cancer in men. J Natl Cancer Inst 2001;93: 1330-6.
World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington DC: AICR, 2007.
