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Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women

Abstract

Objective:

The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women.

Design:

Cross-sectional study.

Setting and subjects:

The population are 2109 women who were control subjects in a case–control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch.

Results:

Serum IGF-I levels were positively related to protein intake (Ptrend<0.001), but not related to energy, fat or carbohydrate intake. Positive relationships were observed with the intake of milk (Ptrend=0.007), calcium (Ptrend<0.001), magnesium (Ptrend=0.003), phosphorus (Ptrend<0.001), potassium (Ptrend=0.002), vitamin B6 (Ptrend=0.03), vitamin B2 (Ptrend=0.001) and inverse relationships with vegetables (Ptrend=0.02) and beta-carotene (Ptrend=0.02). IGFBP-3 was not related with most of the nutrients and foods in this study.

Conclusions:

In this population, circulating IGF-I is modestly related with the intake of protein and minerals, and with milk and cheese, while IGFBP-3 does not appear to be related with diet.

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References

  • Allen NE, Appleby PN, Davey GK, Kaaks R, Rinaldi S, Key TJ (2002). The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans. Cancer Epidemiol Biomarkers Prev 11, 1441–1448.

    CAS  PubMed  Google Scholar 

  • Baibas N, Bamia C, Vassilopoulou E, Sdrolias J, Trichopoulou A, Trichopoulos D (2003). Dietary and lifestyle factors in relation to plasma insulin-like growth factor I in a general population sample. Eur J Cancer Prev 12, 229–234.

    CAS  Article  PubMed  Google Scholar 

  • Bingham S, Riboli E (2004). Diet and cancer – the European prospective investigation into cancer and nutrition. Nat Rev Cancer 4, 206–215.

    CAS  Article  PubMed  Google Scholar 

  • Chan JM, Giovannucci EL (2001). Dairy products, calcium, and vitamin D and risk of prostate cancer. Epidemiol Rev 23, 87–92.

    CAS  Article  PubMed  Google Scholar 

  • Cho E, Smith-Warner SA, Spiegelman D, Beeson WL, van den Brandt PA, Colditz GA et al. (2004). Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies. J Natl Cancer Inst 96, 1015–1022.

    CAS  Article  PubMed  Google Scholar 

  • Clemmons DR, Klibanski A, Underwood LE, McArthur JW, Ridgway EC, Beitins IZ et al. (1981). Reduction of plasma immunoreactive somatomedin C during fasting in humans. J Clin Endocrinol Metab 53, 1247–1250.

    CAS  Article  PubMed  Google Scholar 

  • Daxenberger A, Breier BH, Sauerwein H (1998). Increased milk levels of insulin-like growth factor 1 (IGF-1) for the identification of bovine somatotropin (bST) treated cows. Analyst 123, 2429–2435.

    CAS  Article  PubMed  Google Scholar 

  • DeLellis K, Rinaldi S, Kaaks RJ, Kolonel LN, Henderson B, LeMarchand L (2004). 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 13, 1444–1451.

    CAS  PubMed  Google Scholar 

  • Devine A, Rosen C, Mohan S, Baylink D, Prince RL (1998). Effects of zinc and other nutritional factors on insulin-like growth factor I and insulin-like growth factor binding proteins in postmenopausal women. Am J Clin Nutr 68, 200–206.

    CAS  Article  PubMed  Google Scholar 

  • Douyon L, Schteingart DE (2002). Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. Endocrinol Metab Clin North Am 31, 173–189.

    CAS  Article  PubMed  Google Scholar 

  • Elwood PC, Pickering JE, Hughes J, Fehily AM, Ness AR (2004). Milk drinking, ischaemic heart disease and ischaemic stroke II. Evidence from cohort studies. Eur J Clin Nutr 58, 718–724.

    CAS  Article  PubMed  Google Scholar 

  • Estivariz CF, Ziegler TR (1997). Nutrition and the insulin-like growth factor system. Endocrine 7, 65–71.

    CAS  Article  PubMed  Google Scholar 

  • Ferrari P, Slimani N, Ciampi A, Trichopoulou A, Naska A, Lauria C et al. (2002). Evaluation of under- and overreporting of energy intake in the 24-h diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC). Public Health Nutr 5, 1329–1345.

    CAS  Article  PubMed  Google Scholar 

  • Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM, Semenza GL (2002). Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem 277, 38205–38211.

    CAS  Article  PubMed  Google Scholar 

  • Giovannucci E, Pollak M, Liu Y, Platz EA, Majeed N, Rimm EB et al. (2003). Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men. Cancer Epidemiol Biomark Prev 12, 84–89.

    CAS  Google Scholar 

  • Goodman-Gruen D, Barrett-Connor E (1997). Epidemiology of insulin-like growth factor-I in elderly men and women. The Rancho Bernardo Study. Am J Epidemiol 145, 970–976.

    CAS  Article  PubMed  Google Scholar 

  • Gunnell D, Oliver SE, Peters TJ, Donovan JL, Persad R, Maynard M et al. (2003). Are diet–prostate cancer associations mediated by the IGF axis? A cross-sectional analysis of diet, IGF-I and IGFBP-3 in healthy middle-aged men. Br J Cancer 88, 1682–1686.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Harrela M, Koistinen H, Kaprio J, Lehtovirta M, Tuomilehto J, Eriksson J et al. (1996). Genetic and environmental components of interindividual variation in circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3. J Clin Invest 98, 2612–2615.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Heald AH, Cade JE, Cruickshank JK, Anderson S, White A, Gibson JM (2003). The influence of dietary intake on the insulin-like growth factor (IGF) system across three ethnic groups: a population-based study. Public Health Nutr 6, 175–180.

    CAS  Article  PubMed  Google Scholar 

  • Heaney RP, McCarron DA, Dawson-Hughes B, Oparil S, Berga SL, Stern JS et al. (1999). Dietary changes favorably affect bone remodeling in older adults. J Am Diet Assoc 99, 1228–1233.

    CAS  Article  PubMed  Google Scholar 

  • Holmes MD, Pollak MN, Willett WC, Hankinson SE (2002). Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol Biomark Prev 11, 852–861.

    CAS  Google Scholar 

  • Hong Y, Pedersen NL, Brismar K, Hall K, de Faire U (1996). Quantitative genetic analyses of insulin-like growth factor I (IGF-I), IGF-binding protein-1, and insulin levels in middle-aged and elderly twins. J Clin Endocrinol Metab 81, 1791–1797.

    CAS  PubMed  Google Scholar 

  • Hoppe C, Molgaard C, Juul A, Michaelsen KF (2004). High intakes of skimmed milk, but not meat, increase serum IGF-I and IGFBP-3 in eight-year-old boys. Eur J Clin Nutr 58, 1211–1216.

    CAS  Article  PubMed  Google Scholar 

  • Isley WL, Underwood LE, Clemmons DR (1984). Changes in plasma somatomedin-C in response to ingestion of diets with variable protein and energy content. J Parenteral Enteral Nutr 8, 407–411.

    CAS  Article  Google Scholar 

  • Juskevich JC, Guyer CG (1990). Bovine growth hormone: human food safety evaluation. Science 249, 875–884.

    CAS  Article  PubMed  Google Scholar 

  • Kaaks R, Berrino F, Key T, Rinaldi S, Dossus L, Biessy C et al. (2005). Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 97, 755–765.

    CAS  Article  PubMed  Google Scholar 

  • Kaaks R, Lukanova A (2001). Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc 60, 91–106.

    CAS  Article  PubMed  Google Scholar 

  • Kaklamani VG, Linos A, Kaklamani E, Markaki I, Koumantaki Y, Mantzoros CS (1999). Dietary fat and carbohydrates are independently associated with circulating insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 concentrations in healthy adults. J Clin Oncol 17, 3291–3298.

    CAS  Article  PubMed  Google Scholar 

  • Kaplan RC, Strickler HD, Rohan TE, Muzumdar R, Brown DL (2005). Insulin-like growth factors and coronary heart disease. Cardiol Rev 13, 35–39.

    PubMed  Google Scholar 

  • Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE (2000). The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 21, 215–244.

    CAS  Article  PubMed  Google Scholar 

  • Larsson SC, Wolk K, Brismar K, Wolk A (2005). Association of diet with serum insulin-like growth factor I in middle-aged and elderly men. Am J Clin Nutr 81, 1163–1167.

    CAS  Article  PubMed  Google Scholar 

  • Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM (2005). Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U. S Women Diabetes Care 28, 2926–2932.

    CAS  Article  PubMed  Google Scholar 

  • Ma J, Giovannucci E, Pollak M, Chan JM, Gaziano JM, Willett W et al. (2001). Milk intake, circulating levels of insulin-like growth factor-I, and risk of colorectal cancer in men. J Natl Cancer Inst 93, 1330–1336.

    CAS  Article  PubMed  Google Scholar 

  • Maskarinec G, Takata Y, Kaaks R (2005). The relation between nutritional factors and insulin-like growth factor-I in premenopausal women of different ethnicity. Eur J Nutr 44, 105–113.

    CAS  Article  PubMed  Google Scholar 

  • Mucci LA, Tamimi R, Lagiou P, Trichopoulou A, Benetou V, Spanos E et al. (2001). Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system? BJU Int 87, 814–820.

    CAS  Article  PubMed  Google Scholar 

  • Playford MP, Bicknell D, Bodmer WF, Macaulay VM (2000). Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc Natl Acad Sci USA 97, 12103–12108.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Pollak MN, Schernhammer ES, Hankinson SE (2004). Insulin-like growth factors and neoplasia. Nat Rev Cancer 4, 505–518.

    CAS  Article  PubMed  Google Scholar 

  • Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M (2004). Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363, 1346–1353.

    CAS  Article  PubMed  Google Scholar 

  • Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M et al. (2002). European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 5, 1113–1124.

    CAS  Article  PubMed  Google Scholar 

  • Rudman D, Drinka PJ, Wilson CR, Mattson DE, Scherman F, Cuisinier M et al. (1994). Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men. Clin Endocrinol (Oxf) 40, 653–661.

    CAS  Article  Google Scholar 

  • Sesti G, Sciacqua A, Cardellini M, Marini MA, Maio R, Vatrano M et al. (2005). Plasma concentration of IGF-I is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance. Diabetes Care 28, 120–125.

    CAS  Article  PubMed  Google Scholar 

  • Slimani N, Kaaks R, Ferrari P, Casagrande C, Clavel-Chapelon F, Lotze G et al. (2002). European prospective investigation into cancer and nutrition (EPIC) calibration study: rationale, design and population characteristics. Public Health Nutr 5, 1125–1145.

    CAS  Article  PubMed  Google Scholar 

  • Thissen JP, Ketelslegers JM, Underwood LE (1994). Nutritional regulation of the insulin-like growth factors. Endocr Rev 15, 80–101.

    CAS  PubMed  Google Scholar 

  • Vrieling A, Voskuil DW, Bueno De Mesquita HB, Kaaks R, Van Noord PA, Keinan-Boker L et al. (2004). Dietary determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1, -2 and -3 in women in the Netherlands. Cancer Causes Control 15, 787–796.

    Article  PubMed  Google Scholar 

  • Weissberger AJ, Ho KK, Lazarus L (1991). Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-h growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. J Clin Endocrinol Metab 72, 374–381.

    CAS  Article  PubMed  Google Scholar 

  • Werner H, Le Roith D (2000). New concepts in regulation and function of the insulin-like growth factors: implications for understanding normal growth and neoplasia. Cell Mol Life Sci 57, 932–942.

    CAS  Article  PubMed  Google Scholar 

  • Willett W (2001). Dietary diaries versus food frequency questionnaires – a case of undigestible data. Int J Epidemiol 30, 317–319.

    CAS  Article  PubMed  Google Scholar 

  • Yu H, Berkel H (1999). Insulin-like growth factors and cancer. J La State Med Soc 151, 218–223.

    CAS  PubMed  Google Scholar 

  • Yu H, Rohan T (2000). Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92, 1472–1489.

    CAS  Article  PubMed  Google Scholar 

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Acknowledgements

The work described in this paper was carried out with financial support of the ‘Europe Against Cancer Program’ of the European Commission (SANCO); Danish Cancer Society; German Cancer Aid; Ligue Nationale contre le Cancer, 3M Company, INSERM; German Cancer Research Centre; German Federal Ministry of Education and Research; Dutch Ministry of Public Health, Welfare and Sports; National Cancer Registry and the Regional Cancer Registries Amsterdam, East and Maastricht of The Netherlands; Norwegian Cancer Society; Norwegian Research Council; Health Research Fund (FIS) of the Spanish Ministry of Health; Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra and ISCIII, Red de Centros RCESP, C03/09; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Cancer Research UK; Medical Research Council, UK; Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; Wellcome Trust, UK and the US Army Medical Research and Material Command (DAMD 17-01-0275).

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Correspondence to R Kaaks.

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Guarantor: R Kaaks. Contributors: RK is the principal investigator of the study. TN and LD carried out data analysis. SR conducted the laboratory analyses. The writing team was integrated by TN, LD, SR and RK. All authors contributed to the collection of data, interpretation of results and to the writing of the paper.

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Norat, T., Dossus, L., Rinaldi, S. et al. Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women. Eur J Clin Nutr 61, 91–98 (2007). https://doi.org/10.1038/sj.ejcn.1602494

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  • DOI: https://doi.org/10.1038/sj.ejcn.1602494

Keywords

  • insulin-like growth factor-I
  • insulin-like growth factor binding protein-3
  • diet
  • women
  • protein
  • milk
  • calcium

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