Skip to main content

Advertisement

SpringerLink
Log in

Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA) n repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor–binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study.

Methods

Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5′-exonuclease (Taqman) assay. The IGF-I (CA) n repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression.

Results

The IGF-I (CA) 19 repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)19 repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15–2.73), but not African Americans (OR = 0.73, 95 % CI 0.50–1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28–0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05).

Conclusions

These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics 2008. CA Cancer J Clin 58:71–96

    Article  PubMed  Google Scholar 

  2. Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131(11 suppl):3109S–3120S

    PubMed  CAS  Google Scholar 

  3. Giovannucci E (1995) Insulin and colon cancer. Cancer Causes Control 6:164–179

    Article  PubMed  CAS  Google Scholar 

  4. Keku TO, Lund PK, Galanko J, Simmons JG, Woosley JT, Sandler RS (2005) Insulin resistance, apoptosis, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 14:2076–2081

    Article  PubMed  CAS  Google Scholar 

  5. Le Marchand L, Kolonel LN, Henderson BE, Wilkens LR (2005) Association of an exon 1 polymorphism in the IGFBP3 gene with circulating IGFBP-3 levels and colorectal cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 14:1319–1321

    Article  PubMed  Google Scholar 

  6. Slattery ML, Murtaugh M, Caan B, Ma KN, Neuhausen S, Samowitz W (2005) Energy balance, insulin-related genes and risk of colon and rectal cancer. Int J Cancer 115:148–154

    Article  PubMed  CAS  Google Scholar 

  7. Wernli KJ, Newcomb PA, Wang Y, Makar KW, Shadman M, Chia VM, Burnett-Hartman A, Wurscher MA, Zheng Y, Mandelson MT (2010) Body size, IGF and growth hormone polymorphisms, and colorectal adenomas and hyperplastic polyps. Growth Horm IGF Res 20:305–309

    Article  PubMed  CAS  Google Scholar 

  8. Giovannucci E, Pollak MN, Platz EA, Willet WC, Stampfer MJ, Majeed N, Colditz GA, Speizer FE, Hankinson SE (2000) 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 9:345–349

    PubMed  CAS  Google Scholar 

  9. Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E (2000) Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 92:1592–1600

    Article  PubMed  CAS  Google Scholar 

  10. Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, Stampfer MJ (1999) 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 91:620–625

    Article  PubMed  CAS  Google Scholar 

  11. Nomura AM, Stemmermann GN, Lee J, Pollak MN (2003) Serum insulin-like growth factor I and subsequent risk of colorectal cancer among Japanese–American men. Am J Epidemiol 158:424–431

    Article  PubMed  Google Scholar 

  12. Palmqvist R, Hallmans G, Rinaldi S, Biessy C, Stenling R, Riboli E, Kaaks R (2002) 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 50:642–646

    Article  PubMed  CAS  Google Scholar 

  13. Probst-Hensch NM, Yuan JM, Stanczyk FZ, Gao YT, Ross RK, Yu MC (2001) IGF-1, IGF-2 and IGFBP-3 in prediagnostic serum: association with colorectal cancer in a cohort of Chinese men in Shanghai men. Br J Cancer 85:1695–1699

    Article  PubMed  CAS  Google Scholar 

  14. Gunter MJ, Leitzmann MF (2006) Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes. J Nutr Biochem 17:145–156

    Article  PubMed  CAS  Google Scholar 

  15. Giovannucci E, Pollak M, Platz EA, Willet WC, Stampfer MJ, Majeed N, Colditz GA, Speizer FE, Hankinson SE (2000) Insulin-like growth factor I (IGF-I), IGF-binding protein-3 and the risk of colorectal adenoma and cancer in the Nurses’ Health Study. Growth Horm IGF Res 10(suppl A):S30–S31

    Google Scholar 

  16. Sridhar SS (2009) Insulin–insulin-like growth factor axis and colon cancer. J Clin Oncol 27:165–167

    Article  PubMed  Google Scholar 

  17. McElhom AR, McKnight A-J, Patterson CC, Johnston BT, Hardie LJ, Murray LJ, The Finbar Group (2010) A population-based study of IGF axis polymorphisms and the esophageal inflammation, metaplasia, adenocarcinoma sequence. Gastroenterology 139:204–212

    Article  Google Scholar 

  18. Rotwein P, Pollock KM, Didier DK, Krivi GG (1986) Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides. J Biol Chem 261:4828–4832

    PubMed  CAS  Google Scholar 

  19. DeLellis K, Ingles S, Kolonel L, McKean-Codwin R, Henderson B, Stanczyk F, Probst-Hensch NM (2003) IGF1 genotype, mean plasma level and breast cancer risk in the Hawaii/Los Angeles multiethnic cohort. Br J Cancer 88:277–282

    Article  PubMed  CAS  Google Scholar 

  20. Frayling TM, Hattersley AT, McCarthy A, Holly J, Mitchell SM, Gloyn AL, Owen K, Davies D, Smith GD, Ben-Shlomo Y (2002) A putative functional polymorphism in the IGF-I gene: association studies with type 2 diabetes, adult height, glucose tolerance, and fetal growth in U.K. populations. Diabetes 51:2313–2316

    Article  PubMed  CAS  Google Scholar 

  21. Harrela M, Koistinen H, Kaprio J, Lehtovirta M, Tuomilehto J, Eriksson J, Toivanen L, Koskenuvo M, Leinonen P, Koistinen R, Seppala M (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

    Article  PubMed  CAS  Google Scholar 

  22. Missmer SA, Haiman CA, Hunter DJ, Willet WC, Colditz GA, Speizer FE, Pollak MN, Hankinson SE (2002) A sequence repeat in the insulin-like growth factor-1 gene and risk of breast cancer. Int J Cancer 100:332–336

    Article  PubMed  CAS  Google Scholar 

  23. Rietveld I, Janssen JA, Hofman A, Pols HA, van Duijn CM, Lamberts SW (2003) A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels. Eur J Endocrinol 148:171–175

    Article  PubMed  CAS  Google Scholar 

  24. Rosen CJ, Kurland ES, Vereault D, Adler RA, Rackoff PJ, Craig WY, Witte S, Rogers J, Bilezikian JP (1998) Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density. J Clin Endocrinol Metab 83:2286–2290

    Article  PubMed  CAS  Google Scholar 

  25. Vaessen N, Heutink P, Janssen JA, Witteman JC, Testers L, Hofman A, Lamberts SW, Oostra BA, Pols HA, van Duijn CM (2001) A polymorphism in the gene for IGF-I: functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes 50:637–642

    Article  PubMed  CAS  Google Scholar 

  26. Deal C, Ma J, Wilkin F, Paquette J, Rozen F, Ge B, Hudson T, Stampfer M, Pollak M (2001) Novel promoter polymorphism in insulin-like growth factor-binding protein-3: correlation with serum levels and interaction with known regulators. J Clin Endocrinol Metab 86:1274–1280

    Article  PubMed  CAS  Google Scholar 

  27. Wong HL, Delellis K, Probst-Hensch N, Koh WP, Van Den Berg D, Lee HP, Yu MC, Ingles SA (2005) A new single nucleotide polymorphism in the insulin-like growth factor I regulatory region associates with colorectal cancer risk in Singapore Chinese. Cancer Epidemiol Biomarkers Prev 14:144–151

    PubMed  CAS  Google Scholar 

  28. Zhao R, Berho M, Nogueras J, Sands D, Weiss E, Wexner S, Giardiello FM, Cruz-Correa M (2005) Positive correlation of insulin-like growth factor-II with proliferating cell index in patients with colorectal neoplasia. Cancer Epidemiol Biomarkers Prev 14:1819–1822

    Article  PubMed  CAS  Google Scholar 

  29. Renehan AG, Jones J, Potten CS, Shalet SM, O’Dwyer ST (2000) Elevated serum insulin-like growth factor (IGF)-II and IGF binding protein-2 in patients with colorectal cancer. Br J Cancer 83:1344–1350

    Article  PubMed  CAS  Google Scholar 

  30. Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL, Feinberg AP (2002) Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res 62:6442–6446

    PubMed  CAS  Google Scholar 

  31. Winkler R, Delacroix L, Bensbaho K, Lambert S, Collette J, Hodzic D (1999) IGF-II in primary human colorectal tumors: peptide level, activated promoters, parental imprinting and gene rearrangement. Horm Metab Res 31:148–154

    Article  PubMed  CAS  Google Scholar 

  32. Tadokoro K, Fujii H, Inoue T, Yamada M (1991) Polymerase chain reaction (PCR) for detection of ApaI polymorphism at the insulin like growth factor II gene (IGF2). Nucleic Acids Res 19:6967

    Article  PubMed  CAS  Google Scholar 

  33. Yamauchi T, Kamon J, Minokoshi Y et al (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295

    Article  PubMed  CAS  Google Scholar 

  34. Bacci S, Menzaghi C, Ercolino T, Ma X, Rauseo A, Salvemini L, Vigna C, Fanelli R, Di Mario U, Doria A, Trischitta V (2004) The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients. Diabetes Care 27:2015–2020

    Article  PubMed  CAS  Google Scholar 

  35. Vasseur F, Lepretre F, Lacquemant C, Froguel P (2003) The genetics of adiponectin. Curr Diab Rep 3:151–158

    Article  PubMed  Google Scholar 

  36. Gil-Campos M, Canete RR, Gil A (2004) Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr 23:963–974

    Article  PubMed  CAS  Google Scholar 

  37. Feik E, Baierl A, Hieger B, Führlinger G, Pentz A, Stättner S, Weiss W, Pulgram T, Leeb G, Mach K, Micksche M, Gsur A (2010) Association of IGF1 and IGFBP3 polymorphisms with colorectal polyps and colorectal cancer risk. Cancer Causes Control 21:91–97

    Article  PubMed  Google Scholar 

  38. Wong HL, Koh WP, Probst-Hensch NM, Van den Berg D, Yu MC, Ingles SA (2008) Insulin-like growth factor-1 promoter polymorphisms and colorectal cancer: a functional genomics approach. Gut 57:1090–1096

    Article  PubMed  CAS  Google Scholar 

  39. Slattery ML, Samowitz W, Curtin K, Ma KN, Hoffman M, Caan B, Neuhausen S (2004) Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and colorectal cancer. Cancer Epidemiol Biomarkers Prev 13:1206–1214

    PubMed  CAS  Google Scholar 

  40. He B, Pan Y, Zhang Y, Bao Q, Chen L, Nie Z, Gu L, Xu Y, Wang S (2011) Effects of genetic variations in the adiponectin pathway genes on the risk of colorectal cancer in the Chinese population. BMC Med Genet 12:94

    Article  PubMed  CAS  Google Scholar 

  41. Lin JK, Shen MY, Lin TC, Lan YT, Wang HS, Yang SH, Li AF, Chang SC (2010) Distribution of a single nucleotide polymorphism of insulin-like growth factor-1 in colorectal cancer patients and its association with mucinous adenocarcinoma. Int J Biol Markers 25:195–199

    PubMed  Google Scholar 

  42. Satia JA, Campbell MK, Galanko JA, James A, Carr C, Sandler RS (2004) Longitudinal changes in lifestyle behaviors and health status in colon cancer survivors. Cancer Epidemiol Biomarkers Prev 13:1022

    PubMed  Google Scholar 

  43. Satia JA, Tseng M, Galanko JA, Martin C, Sandler RS (2009) Dietary patterns and colon cancer risk in Whites and African Americans in the North Carolina Colon Cancer Study. Nutr Cancer 61:179–193

    Article  PubMed  Google Scholar 

  44. Butler LM, Millikan RC, Sinha R, Keku TO, Winkel S, Harlan B, Eaton A, Gammon MD, Sandler RS (2008) Modification by N-acetyltransferase 1 genotype on the association between dietary heterocyclic amines and colon cancer in a multiethnic study. Mutat Res 638:162–174

    Article  PubMed  CAS  Google Scholar 

  45. Keku T, Millikan R, Worley K, Winkel S, Eaton A, Biscocho L, Martin C, Sandler R (2002) 5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites. Cancer Epidemiol Biomarkers Prev 11:1611–1621

    PubMed  CAS  Google Scholar 

  46. Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L (1986) A data-based approach to diet questionnaire design and testing. Am J Epidemiol 124:453–469

    PubMed  CAS  Google Scholar 

  47. Block G (1991) Dietary guidelines and the results of food consumption surveys. Am J Clin Nutr 53:356S–357S

    PubMed  CAS  Google Scholar 

  48. Willet WC (1990) Nutritional Epidemiology. Oxford University Press, New York, NY

    Google Scholar 

  49. Collet D (1994) Modeling survival data in medical research. Chapman & Hall, Boca Raton

    Google Scholar 

  50. Hernandez W, Grenade C, Santos ER, Bonilla C, Ahaghotu C, Kittles RA (2007) IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African-Americans. Carcinogenesis 28:2154–2159

    Article  PubMed  CAS  Google Scholar 

  51. Schildkraut JM, Demark-Wahnefried W, Wenham RM, Grubber J, Jeffreys AS, Grambow SC, Marks JR, Moorman PG, Hoyo C, Ali S, Walther PJ (2005) IGF1 (CA)19 repeat and IGFBP3 -202 A/C genotypes and the risk of prostate cancer in Black and White men. Cancer Epidemiol Biomarkers Prev 14:403–408

    Article  PubMed  CAS  Google Scholar 

  52. Takacs I, Koller DL, Peacock M, Christian JC, Hui SL, Conneally PM, Johnston CC Jr, Foround T, Econs MJ (1999) Sibling pair linkage and association studies between bone mineral density and the insulin-like growth factor I gene locus. J Clin Endocrinol Metab 84:4467–4471

    Article  PubMed  CAS  Google Scholar 

  53. Tran N, Bharaj BS, Diamandis EP, Smith M, Li BD, Yu H (2004) Short tandem repeat polymorphism and cancer risk: influence of laboratory analysis on epidemiologic findings. Cancer Epidemiol Biomarkers Prev 13:2133–2140

    PubMed  CAS  Google Scholar 

  54. Ruchat SM, Loos RJ, Rankinen T, Vohl MC, Weisnagel SJ, Després JP, Bouchard C, Pérusse L (2008) Associations between glucose tolerance, insulin sensitivity and insulin secretion phenotypes and polymorphisms in adiponectin and adiponectin receptor genes in the Quebec Family Study. Diabet Med 25:400–406

    Article  PubMed  CAS  Google Scholar 

  55. Gu HF, Abulaiti A, Ostenson CG, Humphreys K, Wahlestedt C, Brookes AJ, Efendic S (2004) Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish caucasians. Diabetes 53:S31–S35

    Article  PubMed  CAS  Google Scholar 

  56. 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

    Article  PubMed  CAS  Google Scholar 

  57. Kao PC, Matheny AP Jr, Lang CA (1994) Insulin-like growth factor-I comparisons in healthy twin children. J Clin Endocrinol Metab 78:310–312

    Article  PubMed  CAS  Google Scholar 

  58. Verhaeghe J, Loos R, Vlietinck R, Herck EV, van Bree R, Schutter AM (1996) C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in cord serum of twins: genetic versus environmental regulation. Am J Obstet Gynecol 175:1180–1188

    Article  PubMed  CAS  Google Scholar 

  59. The International HapMap 3 Consortium (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467:52–58

    Article  Google Scholar 

  60. Morimoto LM, Newcomb PA, White E, Bigler J, Potter JD (2005) Insulin-like growth factor polymorphisms and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 14:1204–1211

    Article  PubMed  CAS  Google Scholar 

  61. Giovannucci E, Haiman CA, Platz EA, Hankinson SE, Pollak MN, Hunter DJ (2002) Dinucleotide repeat in the insulin-like growth factor-I gene is not related to risk of colorectal adenoma. Cancer Epidemiol Biomarkers Prev 11:1509–1510

    PubMed  CAS  Google Scholar 

  62. Hoyo C, Grubber J, Denmark-Wahnefried W, Lobaugh B, Jeffreys AS, Grambow SC, Marks JR, Keku TO, Walther PJ, Shildkraut JM (2009) Predictors of variation in serum IGF-I and IGFBP-3 levels in healthy African American and White men. J Natl Med Assoc 101:711–716

    PubMed  Google Scholar 

  63. Hoyo C, Grubber J, Demark-Wahnefried W, Marks JR, Freedland SJ, Jeffreys AS, Grambow SC, Wenham RM, Walther PJ, Schildkraut JM (2007) Grade-specific prostate cancer associations of IGF1 (CA)19 repeats and IGFBP3-202A/C in blacks and whites. J Natl Med Assoc 99:718–722

    PubMed  Google Scholar 

  64. Chen HY, Chan HIS, Sham ALK, Leung VHK, Ma SL, Ho SC (2011) Haplotype effect in the IGF1 promoter accounts for the association between microsatellite and serum IGF1 concentration. Clin Endocrinol 74:520–527

    Article  CAS  Google Scholar 

  65. Fuchs CS, Goldberg RM, Sargent DJ, Meyerhardt JA, Wolpin BM, Green EM, Pitot HC, Pollak M (2008) Plasma insulin-like growth factors, insulin-like binding protein-3, and outcome in metastatic colorectal cancer: results from intergroup trial N9741. Clin Cancer Res 14:8263–8269

    Article  PubMed  CAS  Google Scholar 

  66. Gallego R, Codony-Serval J, Garcia-Albeniz X, Carcereny E, Longaron R, Oliveras A, Tosca M, Auge JM, Gascon P, Maurel J (2009) Serum IGF-1, IGFBP-3, and matrix metalloproteinase-7 levels and acquired chemo-resistance in advanced colorectal cancer. Endocr Relat Cancer 16:311–317

    Article  PubMed  CAS  Google Scholar 

  67. Cruz-Correa M, Cui H, Giardiello FM, Powe NR, Hylind L, Robinson A, Hutcheon DF, Kafonek DR, Brandenburg S, Wu Y, He X, Feinberg AP (2004) Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition. Gastroenterology 126:964–970

    Article  PubMed  CAS  Google Scholar 

  68. Martinez ME, Giovannucci E, Spiegelman D, Hunter DJ, Willett WC, Colditz GA (1997) Leisure-time physical activity, body size, and colon cancer in women. Nurses’ Health Study Research Group. J Natl Cancer Inst 89:948–955

    Article  PubMed  CAS  Google Scholar 

  69. MacInnis RJ, English DR, Hopper JL, Haydon AM, Gertig DM, Giles GG (2004) Body size and composition and colon cancer risk in men. Cancer Epidemiol Biomarkers Prev 13:553–559

    PubMed  Google Scholar 

  70. Schoen RE, Tangen CM, Kuller LH, Burke GL, Cushman M, Tracy RP, Dobs A, Savage PJ (1999) Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst 91:1147–1154

    Article  PubMed  CAS  Google Scholar 

  71. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953

    Article  PubMed  CAS  Google Scholar 

  72. Filippi E, Sentinelli F, Trischitta V, Romeo S, Arca M, Leonetti F, Di Mario U, Baroni MG (2004) Association of the human adiponectin gene and insulin resistance. Eur J Hum Genet 12:199–205

    Article  PubMed  CAS  Google Scholar 

  73. Kaklamani VG, Wisinski KB, Sadim M, Gulden C, Do A, Offit K, Baron JA, Ahsan H, Mantzoros C, Pasche B (2008) Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA 300:1523–1531

    Article  PubMed  CAS  Google Scholar 

  74. Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE, Trischitta V, Doria A (2002) A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51:2306–2312

    Article  PubMed  CAS  Google Scholar 

  75. Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A (2004) Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 27:2450–2457

    Article  PubMed  CAS  Google Scholar 

  76. Vionnet N, Hani EH, Dupont S, Gallina S, Francke S, Dotte S, De Matos F, Durand E, Lepretre F, Lecoeur F, Gallina P, Zekiri L, Dina C, Froquel P (2000) Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24. Am J Hum Genet 67:1470–1480

    Article  PubMed  CAS  Google Scholar 

  77. Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS (2005) Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst 97:1688–1694

    Article  PubMed  CAS  Google Scholar 

  78. Lukanova A, Soderberg S, Kaaks R, Jellum E, Stattin P (2005) Serum adiponectin is not associated with risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 15:401–402

    Article  Google Scholar 

  79. Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S, Boutin P, Vaxillaire M, Lepretre F, Dupont S, Hara K, Clement K, Bihain B, Kadowaki T, Froquel P (2002) Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 11:2607–2614

    Article  PubMed  CAS  Google Scholar 

  80. Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, Yamauchi T, Otabe S, Okada T, Eto K, Kadowaki H, Hagura R, Akanuma Y, Yazaki Y, Nagai R, Taniyama M, Matsubara K, Yoda M, Nakano Y, Tomita M, Kimura S, Ito C, Froquel P, Kadowaki T (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51:536–540

    Article  PubMed  CAS  Google Scholar 

  81. Wolpin BM, Meyerhardt JA, Chan AT, Ng K, Chan JA, Wu K, Pollak MN, Giovanucc EL, Fuchs CS (2011) Insulin, the insulin-like growth factor axis, and mortality in patients with nonmetastatic colorectal cancer. J Clin Oncol 27:176–185

    Article  Google Scholar 

  82. Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano JM, Stampfer MJ (2004) A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst 96:546–553

    Article  PubMed  CAS  Google Scholar 

  83. Palmqvist R, Stattin P, Rinaldi S, Biessy C, Stenling R, Riboli E, Hallmans G, Kaaks R (2003) Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Int J Cancer 107:89–93

    Article  PubMed  CAS  Google Scholar 

  84. Manousos O, Souglakos J, Bosetti C, Tzonou A, Chatzidakis V, Trichopoulos D, Adami HO, Mantzoros C (1999) IGF-I and IGF-II in relation to colorectal cancer. Int J Cancer 83:15–17

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project was supported in part by grants from the National Institutes of Health K01 CA93654, P30 DK 034987 and R01 CA 66635, P50 CA 106991 and the Howard Hughes Medical Institute (HHMI) support for the UNC Program in Minority access to Biomedical Science (PMABs).

Author information

Authors and Affiliations

  1. Department of Medicine, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, CB#7032, 7430-C Medical Biomolecular Research Building, Chapel Hill, NC, 27599-7032, USA

    Temitope O. Keku, Oluwaseun Omofoye, Maya McDoom, Joseph Galanko & Robert S. Sandler

  2. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA

    Adriana Vidal & Catherine Hoyo

  3. Johnson Smith University, Charlotte, NC, USA

    Shannon Oliver

  4. Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA

    Ingrid J. Hall

  5. Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA

    Kendra Worley & Robert Millikan

Authors
  1. Temitope O. Keku
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adriana Vidal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shannon Oliver
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Catherine Hoyo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ingrid J. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Oluwaseun Omofoye
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maya McDoom
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kendra Worley
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joseph Galanko
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Robert S. Sandler
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Robert Millikan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Temitope O. Keku.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keku, T.O., Vidal, A., Oliver, S. et al. Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites. Cancer Causes Control 23, 1127–1138 (2012). https://doi.org/10.1007/s10552-012-9981-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-012-9981-2

Keywords

Search

Navigation