Abstract
High serum levels of insulin-like growth factor I (IGF-I) are associated with an increased risk of sporadic breast cancer (BC). The aim of the present work is to evaluate the association between IGF-I and hereditary BC risk, using a case–control approach. The work represents an “ad interim” cross-sectional analysis of an ongoing study with a prospective design whose aim is to recruit a cohort of women belonging to high genetic risk families to test potential modulators of penetrance and prognosis. The odd of exposure to high serum IGF-I levels among women with a previous diagnosis of BC (“cases”) was compared with the odd among unaffected “controls”. The odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression, controlling for confounders. We analysed 308 women (209 cases and 99 controls) at high genetic risk of BC. The adjusted OR of BC for the upper tertile of serum IGF-I versus the lowest one was 3.5 (95%CI 1.4–8.8). Excluding from the analysis 64 women under current Tamoxifen or GnRH analogues treatment, the adjusted OR of BC became 3.7 (95%CI 1.4–9.9). The association became stronger restricting the analysis to the 161 women (97 cases and 64 controls) with a proven BRCA mutation. If confirmed by a prospective approach, the association between IGF-I and familial BC will open further options for reducing BC risk in susceptible women.
Similar content being viewed by others
References
Endogenous Hormones and Breast Cancer Collaborative Group (2010) Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 11:530–542
Campagnoli C, Pasanisi P, Peris C, Berrino F (2008) Insulin-like growth factor-I and breast cancer: epidemiological and clinical data. In: Pasqualini JR (ed) Breast cancer: prognosis, treatment and prevention 2nd Edn. Paris: INFORMA-Healthcare. New York, London
Dickson R (1996) Biochemical control of breast development. In: Harris JR, Lippman ME, Morrow M, Hellman S (eds) Diseases of the breast. Lippincott-Raven, Philadelphia
Stewart CE, Rotwein P (1996) Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev 76:1005–1026
Oh JS, Kucab JE, Bushel PR et al (2002) Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells. Neoplasia 4:204–217
Baxter RC, Butt AJ, Schedlich LJ et al (2000) Antiproliferative and pro-apoptotic activities of insulin-like growth factor-binding protein-3. Growth Horm IGF Res 10((Suppl A)):S10–S11
Conover CA (1996) Regulation and physiological role of insulin-like growth factor binding proteins. Endocr J 43(Suppl):S43–S48
Kaaks R (1996) Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control 7:605–625
Eliassen AH, Missmer SA, Tworoger SS et al (2006) Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst 98:1406–1415
Kaaks R, Rinaldi S, Key TJ et al (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12:1071–1082
Kaaks R, Berrino F, Key T 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
Key T, Appleby P, Barnes I et al (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616
Micheli A, Muti P, Secreto G et al (2004) Endogenous sex hormones and subsequent breast cancer in premenopausal women. Int J Cancer 112:312–318
Lautenbach A, Budde A, Wrann CD et al (2009) Obesity and the associated mediators leptin, estrogen and IGF-I enhance the cell proliferation and early tumorigenesis of breast cancer cells. Nutr Cancer 61:484–491
Liebens FP, Carly B, Pastijn A et al (2007) Management of BRCA1/2 associated breast cancer: a systematic qualitative review of the state of knowledge in 2006. Eur J Cancer 43:238–257
The Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91:1310–1316
Brose MS, Rebbeck TR, Calzone KA et al (2002) Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94:1365–1372
Easton DF, Bishop DT, Ford D et al (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet 52:678–701
Ford D, Easton DF, Stratton M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62:676–689
Narod S, Ford D, Devilee P et al (1995) Genetic heterogeneity of breast-ovarian cancer revisited. Breast Cancer Linkage Consortium. Am J Hum Genet 57:957–958
Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases (2000) Anglian Breast Cancer Study Group. Br J Cancer 83:1301–1308
Bonadona V, Sinilnikova OM, Chopin S et al (2005) Contribution of BRCA1 and BRCA2 germ-line mutations to the incidence of breast cancer in young women: results from a prospective population-based study in France. Genes Chromosomes Cancer 43:404–413
Hopper JL, Southey MC, Dite GS et al (1999) Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study. Cancer Epidemiol Biomarkers Prev 8:741–747
Loman N, Bladstrom A, Johannsson O et al (2003) Cancer incidence in relatives of a population-based set of cases of early-onset breast cancer with a known BRCA1 and BRCA2 mutation status. Breast Cancer Res 5:R175–R186
Peto J, Collins N, Barfoot R et al (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 91:943–949
Risch HA, McLaughlin JR, Cole DE et al (2006) Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst 98:1694–1706
Thorlacius S, Struewing JP, Hartge P et al (1998) Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 352:1337–1339
Nkondjock A, Robidoux A, Paredes Y et al (2006) Diet, lifestyle and BRCA-related breast cancer risk among French-Canadians. Breast Cancer Res Treat 98:285–294
Berrino F, Pasanisi P, Berrino J et al (2002) A European case-only study on familial breast cancer. IARC Sci Publ 156:63–65
Pasanisi P, Berrino J, Fusconi E et al (2005) A European Case-Only Study (COS) on familial breast cancer. J Nutr 135:3040S–3041S
Pasanisi P, Hedelin G, Berrino J et al (2009) Oral contraceptive use and BRCA penetrance: a case-only study. Cancer Epidemiol Biomarkers Prev 18:2107–2113
Hoppe C, Udam TR, Lauritzen L et al (2004) Animal protein intake, serum insulin-like growth factor I, and growth in healthy 2.5-year-old Danish children. Am J Clin Nutr 80:447–452
Hoppe C, Molgaard C, Vaag A et al (2005) High intakes of milk, but not meat, increase s-insulin and insulin resistance in 8-year-old boys. Eur J Clin Nutr 59:393–398
Norat T, Dossus L, Rinaldi S et al (2007) Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women. Eur J Clin Nutr 61:91–98
Holmes MD, Pollak MN, Willett WC et al (2002) Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol Biomarkers Prev 11:852–861
Maor S, Papa MZ, Yarden RI et al (2007) Insulin-like growth factor-I controls BRCA1 gene expression through activation of transcription factor Sp1. Horm Metab Res 39:179–185
Maor S, Yosepovich A, Papa MZ et al (2007) Elevated insulin-like growth factor-I receptor (IGF-IR) levels in primary breast tumors associated with BRCA1 mutation. Cancer Lett 257:236–243
Hudelist G, Wagner T, Rosner M et al (2007) Intratumoral IGF-I protein expression is selectively upregulated in breast cancer patients with BRCA1/2 mutations. Endocr Relat Cancer 14:1053–1062
Berry DA, Parmigiani G, Sanchez J et al (1997) Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history. J Natl Cancer Inst 89:227–238
Parmigiani G, Berry D, Aguilar O (1998) Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 62:145–158
Capocaccia R, Verdecchia A, Micheli A et al (1990) Breast cancer incidence and prevalence estimated from survival and mortality. Cancer Causes Control 1:23–29
Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130
Chang-Claude J, Becher H, Eby N et al (1997) Modifying effect of reproductive risk factors on the age at onset of breast cancer for German BRCA1 mutation carriers. J Cancer Res Clin Oncol 123:272–279
Narod SA, Goldgar D, Cannon-Albright L et al (1995) Risk modifiers in carriers of BRCA1 mutations. Int J Cancer 64:394–398
Narod SA (2006) Modifiers of risk of hereditary breast cancer. Oncogene 25:5832–5836
De Angelis G, De Angelis R, Frova L et al (1994) MIAMOD: a computer package to estimate chronic disease morbidity using mortality and survival data. Comput Methods Programs Biomed 44:99–107
Verdecchia A, Capocaccia R, Egidi V et al (1989) A method for the estimation of chronic disease morbidity and trends from mortality data. Stat Med 8:201–216
Roudgari H, Miedzybrodzka ZH, Haites NE (2008) Probability estimation models for prediction of BRCA1 and BRCA2 mutation carriers: COS compares favourably with other models. Fam Cancer 7:199–212
Decensi A, Gandini S, Serrano D et al (2007) Randomized dose-ranging trial of tamoxifen at low doses in hormone replacement therapy users. J Clin Oncol 25:4201–4209
Jernstrom H, Sandberg T, Bageman E et al (2005) Insulin-like growth factor-1 (IGF1) genotype predicts breast volume after pregnancy and hormonal contraception and is associated with circulating IGF-1 levels: implications for risk of early-onset breast cancer in young women from hereditary breast cancer families. Br J Cancer 92:857–866
Phelan CM, Rebbeck TR, Weber BL et al (1996) Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus. Nat Genet 12:309–311
Rebbeck TR, Kantoff PW, Krithivas K et al (1999) Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat. Am J Hum Genet 64:1371–1377
Runnebaum IB, Wang-Gohrke S, Vesprini D et al (2001) Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives. Pharmacogenetics 11:635–638
Pasanisi P, Venturelli E, Morelli D et al (2008) Serum insulin-like growth factor-I and platelet-derived growth factor as biomarkers of breast cancer prognosis. Cancer Epidemiol Biomarkers Prev 17:1719–1722
Kurek R, Tunn UW, Eckart O et al (2000) The significance of serum levels of insulin-like growth factor-1 in patients with prostate cancer. BJU Int 85:125–129
Muller J, Juul A, Andersson AM et al (2000) Hormonal changes during GnRH analogue therapy in children with central precocious puberty. J Pediatr Endocrinol Metab 13(Suppl 1):739–1746
Chen S, Iversen ES, Friebel T et al (2006) Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 24:863–871
Jatoi I, Anderson WF (2008) Management of women who have a genetic predisposition for breast cancer. Surg Clin North Am 88:845–861
Roukos DH, Briasoulis E (2007) Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome. Nat Clin Pract Oncol 4:578–590
Gronwald J, Tung N, Foulkes WD et al (2006) Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 118:2281–2284
Reding KW, Bernstein JL, Langholz BM et al (2010) Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer. Breast Cancer Res Treat 23:491–498
Kotsopoulos J, Narod SA (2005) Towards a dietary prevention of hereditary breast cancer. Cancer Causes Control 16:125–138
Nkondjock A, Robidoux A, Paredes Y et al (2006) Diet, lifestyle and BRCA-related breast cancer risk among French-Canadians. Breast Cancer Res Treat 98:2852–2894
King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302:643–646
Berrino F, Villarini A, De Petris M et al (2006) Adjuvant diet to improve hormonal and metabolic factors affecting breast cancer prognosis. Ann N Y Acad Sci 1089:110–118
Fontana L, Klein S, Holloszy JO (2006) Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk. Am J Clin Nutr 84:1456–1462
Irwin ML, Varma K, Alvarez-Reeves M et al (2009) Randomized controlled trial of aerobic exercise on insulin and insulin-like growth factors in breast cancer survivors: the Yale Exercise and Survivorship study. Cancer Epidemiol Biomarkers Prev 18:306–313
Berrino F, Bellati C, Secreto G et al (2001) Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. Cancer Epidemiol Biomarkers Prev 10:25–33
Berrino F, Pasanisi P, Bellati C et al (2005) Serum testosterone levels and breast cancer recurrence. Int J Cancer 113:499–502
Kaaks R, Bellati C, Venturelli E et al (2003) 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 57:1079–1088
Pasanisi P, Berrino F, De Petris M et al (2006) Metabolic syndrome as a prognostic factor for breast cancer recurrences. Int J Cancer 119:236–238
Acknowledgments
We thank Mrs. Maria Grazia Guerrini for the editorial support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pasanisi, P., Bruno, E., Venturelli, E. et al. Serum levels of IGF-I and BRCA penetrance: a case control study in breast cancer families. Familial Cancer 10, 521–528 (2011). https://doi.org/10.1007/s10689-011-9437-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-011-9437-y