title: Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies.
abstract: BACKGROUND
  Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Some published results have shown an association between circulating IGF1 and breast-cancer risk, but it has been unclear whether this relationship is consistent or whether it is modified by IGF binding protein 3 (IGFBP3), menopausal status, oestrogen receptor status or other factors. The relationship of IGF1 (and IGFBP3) with breast-cancer risk factors is also unclear. The Endogenous Hormones and Breast Cancer Collaborative Group was established to analyse pooled individual data from prospective studies to increase the precision of the estimated associations of endogenous hormones with breast-cancer risk.
  
  
  METHODS
  Individual data on prediagnostic IGF1 and IGFBP3 concentrations were obtained from 17 prospective studies in 12 countries. The associations of IGF1 with risk factors for breast cancer in controls were examined by calculating geometric mean concentrations in categories of these factors. The odds ratios (ORs) with 95% CIs of breast cancer associated with increasing IGF1 concentrations were estimated by conditional logistic regression in 4790 cases and 9428 matched controls, with stratification by study, age at baseline, and date of baseline. All statistical tests were two-sided, and a p value of less than 0.05 was considered significant.
  
  
  RESULTS
  IGF1 concentrations, adjusted for age, were positively associated with height and age at first pregnancy, inversely associated with age at menarche and years since menopause, and were higher in moderately overweight women and moderate alcohol consumers than in other women. The OR for breast cancer for women in the highest versus the lowest fifth of IGF1 concentration was 1.28 (95% CI 1.14-1.44; p<0.0001). This association was not altered by adjusting for IGFBP3, and did not vary significantly by menopausal status at blood collection. The ORs for a difference in IGF1 concentration between the highest and lowest fifth were 1.38 (95% CI 1.14-1.68) for oestrogen-receptor-positive tumours and 0.80 (0.57-1.13) for oestrogen-receptor-negative tumours (p for heterogeneity=0.007).
  
  
  CONCLUSIONS
  Circulating IGF1 is positively associated with breast-cancer risk. The association is not substantially modified by IGFBP3, and does not differ markedly by menopausal status, but seems to be confined to oestrogen-receptor-positive tumours.
  
  
  BACKGROUND
  Cancer Research UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.forename: Paul N
authors.initials: PN
authors.lastname: Appleby
authors.forename: Gillian K
authors.initials: GK
authors.lastname: Reeves
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roddam
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008593:Menopause; D008875:Middle Aged; D016017:Odds Ratio; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D011960:Receptors, Estrogen; D007334:Insulin-Like Growth Factor I
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):739-46
references.pmid: 12917205
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1361-8
references.pmid: 12433712
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1333-40
references.pmid: 19423514
references.citation: J Clin Endocrinol Metab. 2008 Jul;93(7):2539-45
references.pmid: 18397983
references.citation: Horm Res. 2003;60(2):53-60
references.pmid: 12876414
references.citation: J Natl Cancer Inst. 2004 Dec 15;96(24):1856-65
references.pmid: 15601642
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):699-704
references.pmid: 15767352
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1444-51
references.pmid: 15342444
references.citation: Endocr Relat Cancer. 2005 Dec;12(4):1071-82
references.pmid: 16322344
references.citation: Breast Cancer Res Treat. 2004 Nov;88(1):63-73
references.pmid: 15538047
references.citation: Endocr Rev. 2007 Feb;28(1):20-47
references.pmid: 16931767
references.citation: Nat Rev Cancer. 2008 Dec;8(12):915-28
references.pmid: 19029956
references.citation: Br J Cancer. 2004 Oct 18;91(8):1525-31
references.pmid: 15354219
references.citation: Eur J Cancer. 1993;29A(4):492-7
references.pmid: 8435198
references.citation: Eur J Endocrinol. 2009 Nov;161(5):705-13
references.pmid: 19690083
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):763-8
references.pmid: 17416768
references.citation: J Natl Cancer Inst. 2009 Jan 7;101(1):48-60
references.pmid: 19116382
references.citation: Cancer Res. 1984 May;44(5):2122-8
references.pmid: 6324997
references.citation: Cancer Causes Control. 2005 Oct;16(8):917-27
references.pmid: 16132801
references.citation: Endocr Relat Cancer. 2006 Jun;13(2):583-92
references.pmid: 16728584
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):48-52
references.pmid: 15668475
references.citation: J Exp Clin Cancer Res. 2004 Sep;23(3):385-94
references.pmid: 15595626
references.citation: J Natl Cancer Inst. 2000 Oct 4;92(19):1592-600
references.pmid: 11018095
references.citation: Int J Cancer. 2003 Aug 10;106(1):90-5
references.pmid: 12794762
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Sep;11(9):852-61
references.pmid: 12223429
references.citation: Cancer Epidemiol Biomarkers Prev. 2001 Apr;10(4):377-84
references.pmid: 11319179
references.citation: Horm Res. 2004;62 Suppl 1:8-16
references.pmid: 15761227
references.citation: Eur J Cancer Prev. 2005 Dec;14(6):493-6
references.pmid: 16284492
references.citation: J Natl Cancer Inst. 2002 Apr 17;94(8):606-16
references.pmid: 11959894
references.citation: Cancer Lett. 1987 Dec;38(1-2):223-30
references.pmid: 2961436
references.citation: J Clin Oncol. 1999 Mar;17(3):813-7
references.pmid: 10071271
references.citation: Int J Cancer. 2006 Mar 1;118(5):1279-84
references.pmid: 16161053
references.citation: Am J Epidemiol. 1997 Jun 1;145(11):970-6
references.pmid: 9169905
references.citation: Horm Cancer. 2010 Apr;1(2):100-11
references.pmid: 21761353
references.citation: Endocr Rev. 2002 Dec;23(6):824-54
references.pmid: 12466191
references.citation: J Natl Cancer Inst. 2006 Oct 4;98(19):1406-15
references.pmid: 17018787
references.citation: Lancet. 1998 May 9;351(9113):1393-6
references.pmid: 9593409
references.citation: Ann Intern Med. 1999 Feb 16;130(4 Pt 1):270-7
references.pmid: 10068384
references.citation: Clin Endocrinol Metab. 1984 Mar;13(1):113-43
references.pmid: 6202444
references.citation: Eur J Cancer Prev. 2001 Oct;10(5):443-52
references.pmid: 11711759
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1759-64
references.pmid: 15533904
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):960-5
references.pmid: 20233851
references.citation: Int J Cancer. 2006 Jun 1;118(11):2863-5
references.pmid: 16381008
references.citation: J Endocrinol. 2006 Dec;191(3):605-12
references.pmid: 17170218
references.citation: Endocr Relat Cancer. 2006 Jun;13(2):593-605
references.pmid: 16728585
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):2264-7
references.pmid: 15598790
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):2097-100
references.pmid: 18708402
references.citation: Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):972-8
references.pmid: 16702379
references.citation: Am J Clin Nutr. 2005 Feb;81(2):503-7
references.pmid: 15699241
references.citation: Endocr Relat Cancer. 2007 Sep;14(3):721-32
references.pmid: 17914102
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1566-73
references.pmid: 12496045
references.citation: Int J Cancer. 2000 Dec 1;88(5):828-32
references.pmid: 11072255
references.citation: Pituitary. 2007;10(2):129-33
references.pmid: 17487588
references.citation: Cancer Causes Control. 2002 May;13(4):307-16
references.pmid: 12074500
references.citation: Mol Pathol. 2001 Jun;54(3):149-54
references.pmid: 11376126
references.citation: Clin Chem. 2002 Dec;48(12):2248-51
references.pmid: 12446484
references.citation: Cancer Causes Control. 2002 Aug;13(6):509-16
references.pmid: 12195640
references.citation: Br J Cancer. 2005 Apr 11;92(7):1283-7
references.pmid: 15756268
references.citation: Endocr Relat Cancer. 2006 Jun;13(2):273-8
references.pmid: 16728563
references.citation: J Mammary Gland Biol Neoplasia. 2008 Dec;13(4):455-69
references.pmid: 19031049