Skip to main content

Advertisement

SpringerLink
Log in

Genetic variation in insulin pathway genes and distal colorectal adenoma risk

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

Insulin, glucose, and other insulin-related proteins that mediate insulin signaling are associated with colorectal neoplasia risk, but associations with common genetic variation in insulin axis genes are less clear. In this study, we used a comprehensive tag single-nucleotide polymorphisms (SNPs) approach to define genetic variation in six insulin axis genes (IGF1, IGF2, IGFBP1, IGFBP3, IRS1, and IRS2) and three genes associated with estrogen signaling (ESR1, ESR2, and PGR).

Methods

We assessed associations between SNPs and distal colorectal adenoma (CRA) risk in a case–control study of 1,351 subjects. Cases were individuals with one or more adenomas diagnosed during sigmoidoscopy, and controls were individuals with no adenomas at the sigmoidoscopy exam. We used unconditional logistic regression assuming an additive model to assess SNP-specific risks adjusting for multiple comparisons with P act.

Results

Distal adenoma risk was significantly increased for one SNP in IGF2 [per minor allele OR = 1.41; 95 % confidence interval (CI) = 1.16, 1.67; P act = 0.005] and decreased for an ESR2 SNP (per minor allele OR = 0.78; 95 % CI = 0.66, 0.91; P act = 0.041). There was no statistically significant heterogeneity of these associations by race, sex, BMI, physical activity, or, in women, hormone replacement therapy use. Risk estimates did not differ in the colon versus rectum or for smaller (<1 cm) versus larger (>1 cm) adenomas.

Conclusions

These data suggest that selected genetic variability in IGF2 and ESR2 may be modifiers of CRA risk.

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. Komninou D, Ayonote A, Richie JP Jr, Rigas B (2003) Insulin resistance and its contribution to colon carcinogenesis. Exp Biol Med (Maywood) 228(4):396–405

    CAS  Google Scholar 

  2. Giovannucci E (1995) Insulin and colon cancer. Cancer Causes Control 6(2):164–179

    Article  PubMed  CAS  Google Scholar 

  3. McKeown-Eyssen G (1994) Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev 3(8):687–695

    PubMed  CAS  Google Scholar 

  4. Gunter MJ, Hayes RB, Chatterjee N, Yeager M, Welch R, Schoen RE, Yakochi L, Schatzkin A, Peters U (2007) Insulin resistance-related genes and advanced left-sided colorectal adenoma. Cancer Epidemiol Biomarkers Prev 16(4):703–708

    Article  PubMed  CAS  Google Scholar 

  5. LeRoy EC, Moore JH, Hu C, Martinez ME, Lance P, Duggan D, Thompson PA (2011) Genes in the insulin and insulin-like growth factor pathway and odds of metachronous colorectal neoplasia. Hum Genet 129(5):503–512

    Article  PubMed  CAS  Google Scholar 

  6. Pechlivanis S, Pardini B, Bermejo JL, Wagner K, Naccarati A, Vodickova L, Novotny J, Hemminki K, Vodicka P, Forsti A (2007) Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect. Endocr Relat Cancer 14(3):733–740

    Article  PubMed  CAS  Google Scholar 

  7. 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(7):1206–1214

    PubMed  CAS  Google Scholar 

  8. 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(4):305–309

    Article  PubMed  CAS  Google Scholar 

  9. Chen MJ, Longnecker MP, Morgenstern H, Lee ER, Frankl HD, Haile RW (1998) Recent use of hormone replacement therapy and the prevalence of colorectal adenomas. Cancer Epidemiol Biomarkers Prev 7(3):227–230

    PubMed  CAS  Google Scholar 

  10. Grodstein F, Martinez ME, Platz EA, Giovannucci E, Colditz GA, Kautzky M, Fuchs C, Stampfer MJ (1998) Postmenopausal hormone use and risk for colorectal cancer and adenoma. Ann Intern Med 128(9):705–712

    PubMed  CAS  Google Scholar 

  11. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD (2002) Postmenopausal hormone replacement therapy: scientific review. JAMA 288(7):872–881

    Article  PubMed  CAS  Google Scholar 

  12. Potter JD, Bostick RM, Grandits GA, Fosdick L, Elmer P, Wood J, Grambsch P, Louis TA (1996) Hormone replacement therapy is associated with lower risk of adenomatous polyps of the large bowel: the Minnesota Cancer Prevention Research Unit Case–Control Study. Cancer Epidemiol Biomarkers Prev 5(10):779–784

    PubMed  CAS  Google Scholar 

  13. Purdue MP, Mink PJ, Hartge P, Huang WY, Buys S, Hayes RB (2005) Hormone replacement therapy, reproductive history, and colorectal adenomas: data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (United States). Cancer Causes Control 16(8):965–973

    Article  PubMed  Google Scholar 

  14. Terry MB, Neugut AI, Bostick RM, Sandler RS, Haile RW, Jacobson JS, Fenoglio-Preiser CM, Potter JD (2002) Risk factors for advanced colorectal adenomas: a pooled analysis. Cancer Epidemiol Biomarkers Prev 11(7):622–629

    PubMed  Google Scholar 

  15. Barros RP, Machado UF, Gustafsson JA (2006) Estrogen receptors: new players in diabetes mellitus. Trends Mol Med 12(9):425–431

    Article  PubMed  CAS  Google Scholar 

  16. Brown LM, Gent L, Davis K, Clegg DJ (2010) Metabolic impact of sex hormones on obesity. Brain Res 1350:77–85

    Article  PubMed  CAS  Google Scholar 

  17. Kennelly R, Kavanagh DO, Hogan AM, Winter DC (2008) Oestrogen and the colon: potential mechanisms for cancer prevention. Lancet Oncol 9(4):385–391

    Article  PubMed  CAS  Google Scholar 

  18. Rondini EA, Harvey AE, Steibel JP, Hursting SD, Fenton JI (2011) Energy balance modulates colon tumor growth: interactive roles of insulin and estrogen. Mol Carcinog 50(5):370–382

    Article  PubMed  CAS  Google Scholar 

  19. Yakar S, Nunez NP, Pennisi P, Brodt P, Sun H, Fallavollita L, Zhao H, Scavo L, Novosyadlyy R, Kurshan N, Stannard B, East-Palmer J, Smith NC, Perkins SN, Fuchs-Young R, Barrett JC, Hursting SD, LeRoith D (2006) Increased tumor growth in mice with diet-induced obesity: impact of ovarian hormones. Endocrinology 147(12):5826–5834

    Article  PubMed  CAS  Google Scholar 

  20. Leung KC, Xu A, Craig ME, Martin A, Lam KS, O'Sullivan AJ (2009) Adiponectin isoform distribution in women—relationship to female sex steroids and insulin sensitivity. Metabolism 58(2):239–245

    Article  PubMed  CAS  Google Scholar 

  21. Salpeter SR, Walsh JM, Ormiston TM, Greyber E, Buckley NS, Salpeter EE (2006) Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab 8(5):538–554

    Article  PubMed  CAS  Google Scholar 

  22. 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, Xue X, Harris TG, Burk RD, Strickler HD (2008) Insulin, insulin-like growth factor-I, endogenous estradiol, and risk of colorectal cancer in postmenopausal women. Cancer Res 68(1):329–337

    Article  PubMed  CAS  Google Scholar 

  23. Lin J, Zee RY, Liu KY, Zhang SM, Lee IM, Manson JE, Giovannucci E, Buring JE, Cook NR (2010) Genetic variation in sex-steroid receptors and synthesizing enzymes and colorectal cancer risk in women. Cancer Causes Control 21(6):897–908

    Article  PubMed  Google Scholar 

  24. Rudolph A, Sainz J, Hein R, Hoffmeister M, Frank B, Forsti A, Brenner H, Hemminki K, Chang-Claude J (2011) Modification of menopausal hormone therapy-associated colorectal cancer risk by polymorphisms in sex steroid signaling, metabolism and transport related genes. Endocr Relat Cancer 18(3):371–384

    Article  PubMed  CAS  Google Scholar 

  25. Sainz J, Rudolph A, Hein R, Hoffmeister M, Buch S, von Schonfels W, Hampe J, Schafmayer C, Volzke H, Frank B, Brenner H, Forsti A, Hemminki K, Chang-Claude J (2011) Association of genetic polymorphisms in ESR2, HSD17B1, ABCB1, and SHBG genes with colorectal cancer risk. Endocr Relat Cancer 18(2):265–276

    Article  PubMed  CAS  Google Scholar 

  26. Slattery ML, Sweeney C, Murtaugh M, Ma KN, Wolff RK, Potter JD, Caan BJ, Samowitz W (2005) Associations between ERalpha, ERbeta, and AR genotypes and colon and rectal cancer. Cancer Epidemiol Biomarkers Prev 14(12):2936–2942

    Article  PubMed  CAS  Google Scholar 

  27. Stern MC, Siegmund KD, Conti DV, Corral R, Haile RW (2006) XRCC1, XRCC3, and XPD polymorphisms as modifiers of the effect of smoking and alcohol on colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 15(12):2384–2390

    Article  PubMed  CAS  Google Scholar 

  28. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC (1992) Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol 135(10):1114–1126, discussion 1127–1136

    PubMed  CAS  Google Scholar 

  29. Stram DO, Hankin JH, Wilkens LR, Pike MC, Monroe KR, Park S, Henderson BE, Nomura AM, Earle ME, Nagamine FS, Kolonel LN (2000) Calibration of the dietary questionnaire for a multiethnic cohort in Hawaii and Los Angeles. Am J Epidemiol 151(4):358–370

    Article  PubMed  CAS  Google Scholar 

  30. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265

    Article  PubMed  CAS  Google Scholar 

  31. Shen R, Fan JB, Campbell D, Chang W, Chen J, Doucet D, Yeakley J, Bibikova M, Wickham Garcia E, McBride C, Steemers F, Garcia F, Kermani BG, Gunderson K, Oliphant A (2005) High-throughput SNP genotyping on universal bead arrays. Mutat Res 573(1–2):70–82

    PubMed  CAS  Google Scholar 

  32. Consortium TIH (2005) A haplotype map of the human genome. Nature 437(7063):1299–1320

    Article  Google Scholar 

  33. Levine AJ, Siegmund KD, Ervin CM, Diep A, Lee ER, Frankl HD, Haile RW (2000) The methylenetetrahydrofolate reductase 677C–>T polymorphism and distal colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 9(7):657–663

    PubMed  CAS  Google Scholar 

  34. Conneely KN, Boehnke M (2007) So many correlated tests, so little time! Rapid adjustment of P values for multiple correlated tests. Am J Hum Genet 81(6):1158–1168

    Article  PubMed  CAS  Google Scholar 

  35. Chen X, Guan J, Song Y, Chen P, Zheng H, Tang C, Wu Q (2008) IGF-I (CA) repeat polymorphisms and risk of cancer: a meta-analysis. J Hum Genet 53(3):227–238

    Article  PubMed  CAS  Google Scholar 

  36. Morris JK, George LM, Wu T, Wald NJ (2006) Insulin-like growth factors and cancer: no role in screening. Evidence from the BUPA study and meta-analysis of prospective epidemiological studies. Br J Cancer 95(1):112–117

    Article  PubMed  CAS  Google Scholar 

  37. Pisani P (2008) Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem 114(1):63–70

    Article  PubMed  CAS  Google Scholar 

  38. 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(9418):1346–1353

    Article  PubMed  CAS  Google Scholar 

  39. Rinaldi S, Cleveland R, Norat T, Biessy C, Rohrmann S, Linseisen J, Boeing H, Pischon T, Panico S, Agnoli C, Palli D, Tumino R, Vineis P, Peeters PH, van Gils CH, Bueno-de-Mesquita BH, Vrieling A, Allen NE, Roddam A, Bingham S, Khaw KT, Manjer J, Borgquist S, Dumeaux V, Torhild Gram I, Lund E, Trichopoulou A, Makrygiannis G, Benetou V, Molina E, Donate Suarez I, Barricarte Gurrea A, Gonzalez CA, Tormo MJ, Altzibar JM, Olsen A, Tjonneland A, Gronbaek H, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Morois S, Slimani N, Boffetta P, Jenab M, Riboli E, Kaaks R (2010) Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. Int J Cancer 126(7):1702–1715

    PubMed  CAS  Google Scholar 

  40. Chen W, Wang S, Tian T, Bai J, Hu Z, Xu Y, Dong J, Chen F, Wang X, Shen H (2009) Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies. Eur J Hum Genet 17(12):1668–1675

    Article  PubMed  CAS  Google Scholar 

  41. Li L, Huang X, Huo K (2010) IGFBP3 polymorphisms and risk of cancer: a meta-analysis. Mol Biol Rep 37(1):127–140

    Article  PubMed  Google Scholar 

  42. Pechlivanis S, Wagner K, Chang-Claude J, Hoffmeister M, Brenner H, Forsti A (2007) Polymorphisms in the insulin like growth factor 1 and IGF binding protein 3 genes and risk of colorectal cancer. Cancer Detect Prev 31(5):408–416

    Article  PubMed  CAS  Google Scholar 

  43. Furstenberger G, Senn HJ (2002) Insulin-like growth factors and cancer. Lancet Oncol 3(5):298–302

    Article  PubMed  CAS  Google Scholar 

  44. Hassan AB, Howell JA (2000) Insulin-like growth factor II supply modifies growth of intestinal adenoma in Apc Min/+ mice. Cancer Res 60(4):1070–1076

    PubMed  CAS  Google Scholar 

  45. Kaneda A, Feinberg AP (2005) Loss of imprinting of IGF2: a common epigenetic modifier of intestinal tumor risk. Cancer Res 65(24):11236–11240

    Article  PubMed  CAS  Google Scholar 

  46. Kaneda A, Wang CJ, Cheong R, Timp W, Onyango P, Wen B, Iacobuzio-Donahue CA, Ohlsson R, Andraos R, Pearson MA, Sharov AA, Longo DL, Ko MS, Levchenko A, Feinberg AP (2007) Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci U S A 104(52):20926–20931

    Article  PubMed  CAS  Google Scholar 

  47. Sakatani T, Kaneda A, Iacobuzio-Donahue CA, Carter MG, de Boom WS, Okano H, Ko MS, Ohlsson R, Longo DL, Feinberg AP (2005) Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science 307(5717):1976–1978

    Article  PubMed  CAS  Google Scholar 

  48. Woodson K, Flood A, Green L, Tangrea JA, Hanson J, Cash B, Schatzkin A, Schoenfeld P (2004) Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women. J Natl Cancer Inst 96(5):407–410

    Article  PubMed  CAS  Google Scholar 

  49. Cui H, Horon IL, Ohlsson R, Hamilton SR, Feinberg AP (1998) Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nat Med 4(11):1276–1280

    Article  PubMed  CAS  Google Scholar 

  50. Ito Y, Koessler T, Ibrahim AE, Rai S, Vowler SL, Abu-Amero S, Silva AL, Maia AT, Huddleston JE, Uribe-Lewis S, Woodfine K, Jagodic M, Nativio R, Dunning A, Moore G, Klenova E, Bingham S, Pharoah PD, Brenton JD, Beck S, Sandhu MS, Murrell A (2008) Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer. Hum Mol Genet 17(17):2633–2643

    Article  PubMed  CAS  Google Scholar 

  51. Kinouchi Y, Hiwatashi N, Higashioka S, Nagashima F, Chida M, Toyota T (1996) Relaxation of imprinting of the insulin-like growth factor II gene in colorectal cancer. Cancer Lett 107(1):105–108

    Article  PubMed  CAS  Google Scholar 

  52. Nakagawa H, Chadwick RB, Peltomaki P, Plass C, Nakamura Y, de La Chapelle A (2001) Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer. Proc Natl Acad Sci U S A 98(2):591–596

    Article  PubMed  CAS  Google Scholar 

  53. Nishihara S, Hayashida T, Mitsuya K, Schulz TC, Ikeguchi M, Kaibara N, Oshimura M (2000) Multipoint imprinting analysis in sporadic colorectal cancers with and without microsatellite instability. Int J Oncol 17(2):317–322

    PubMed  CAS  Google Scholar 

  54. Sasaki J, Konishi F, Kawamura YJ, Kai T, Takata O, Tsukamoto T (2006) Clinicopathological characteristics of colorectal cancers with loss of imprinting of insulin-like growth factor 2. Int J Cancer 119(1):80–83

    Article  PubMed  CAS  Google Scholar 

  55. Tanaka K, Shiota G, Meguro M, Mitsuya K, Oshimura M, Kawasaki H (2001) Loss of imprinting of long QT intronic transcript 1 in colorectal cancer. Oncology 60(3):268–273

    Article  PubMed  CAS  Google Scholar 

  56. Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Kafonek DR, Brandenburg S, Wu Y, He X, Powe NR, Feinberg AP (2003) Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299(5613):1753–1755

    Article  PubMed  CAS  Google Scholar 

  57. Liou JM, Wu MS, Lin JT, Wang HP, Huang SP, Chiu HM, Lee YC, Lin YB, Shun CT, Liang JT (2007) Loss of imprinting of insulin-like growth factor II is associated with increased risk of proximal colon cancer. Eur J Cancer 43(8):1276–1282

    Article  PubMed  CAS  Google Scholar 

  58. Kaaks R, Stattin P, Villar S, Poetsch AR, Dossus L, Nieters A, Riboli E, Palmqvist R, Hallmans G, Plass C, Friesen MD (2009) Insulin-like growth factor-II methylation status in lymphocyte DNA and colon cancer risk in the Northern Sweden Health and Disease cohort. Cancer Res 69(13):5400–5405

    Article  PubMed  CAS  Google Scholar 

  59. Foryst-Ludwig A, Kintscher U (2010) Metabolic impact of estrogen signalling through ERalpha and ERbeta. J Steroid Biochem Mol Biol 122(1–3):74–81

    Article  PubMed  CAS  Google Scholar 

  60. Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, Bassford T, Burke G, Torrens J, Howard BV (2004) Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia 47(7):1175–1187

    Article  PubMed  CAS  Google Scholar 

  61. Ribas V, Nguyen MT, Henstridge DC, Nguyen AK, Beaven SW, Watt MJ, Hevener AL (2010) Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERalpha-deficient mice. Am J Physiol Endocrinol Metab 298(2):E304–E319

    Article  PubMed  CAS  Google Scholar 

  62. Barone M, Tanzi S, Lofano K, Scavo MP, Pricci M, Demarinis L, Papagni S, Guido R, Maiorano E, Ingravallo G, Comelli MC, Francavilla A, Di Leo A (2010) Dietary-induced ERbeta upregulation counteracts intestinal neoplasia development in intact male ApcMin/+ mice. Carcinogenesis 31(2):269–274

    Article  PubMed  CAS  Google Scholar 

  63. Hartman J, Edvardsson K, Lindberg K, Zhao C, Williams C, Strom A, Gustafsson JA (2009) Tumor repressive functions of estrogen receptor beta in SW480 colon cancer cells. Cancer Res 69(15):6100–6106

    Article  PubMed  CAS  Google Scholar 

  64. Martineti V, Picariello L, Tognarini I, Carbonell Sala S, Gozzini A, Azzari C, Mavilia C, Tanini A, Falchetti A, Fiorelli G, Tonelli F, Brandi ML (2005) ERbeta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components. Endocr Relat Cancer 12(2):455–469

    Article  PubMed  CAS  Google Scholar 

  65. Wada-Hiraike O, Imamov O, Hiraike H, Hultenby K, Schwend T, Omoto Y, Warner M, Gustafsson JA (2006) Role of estrogen receptor beta in colonic epithelium. Proc Natl Acad Sci U S A 103(8):2959–2964

    Article  PubMed  CAS  Google Scholar 

  66. Weige CC, Allred KF, Allred CD (2009) Estradiol alters cell growth in nonmalignant colonocytes and reduces the formation of preneoplastic lesions in the colon. Cancer Res 69(23):9118–9124

    Article  PubMed  CAS  Google Scholar 

  67. Honma N, Arai T, Takubo K, Younes M, Tanaka N, Mieno MN, Tamura K, Ikeda S, Sawabe M, Muramatsu M (2011) Oestrogen receptor-beta CA repeat polymorphism is associated with incidence of colorectal cancer among females. Histopathology 59(2):216–224

    PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank all the subjects who contributed their time to this study. We would also like to thank Terry Kolb and Jessie Lin for their assistance with data collection, cleaning and management and Anh Diep and for her assistance with biospecimen management. This work was supported by the National Cancer Institute, National Institutes of Health under 1R01 CA096830 and 5P01 CA42710.

Potential conflicts of interest

No authors report any conflict of interest. The content of the manuscript does not necessarily reflect the views or policies of the National Cancer Institute nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Author information

Authors and Affiliations

  1. Department of Preventive Medicine, Genetic Epidemiology, University of Southern California Keck School of Medicine, NRT 1450 Biggy Street Room 1509A, Los Angeles, CA, 90033, USA

    A. Joan Levine, Ugonna Ihenacho, Won Lee, Jane C. Figueiredo, David J. Vandenberg, Christopher K. Edlund, Brian D. Davis, Mariana C. Stern & Robert W. Haile

Authors
  1. A. Joan Levine
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ugonna Ihenacho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Won Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jane C. Figueiredo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David J. Vandenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christopher K. Edlund
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brian D. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mariana C. Stern
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Robert W. Haile
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Joan Levine.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1

Genotype effects by race (XLSX 267 kb)

Supplementary Table 2

Genotype effects by sex (XLSX 104 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Levine, A.J., Ihenacho, U., Lee, W. et al. Genetic variation in insulin pathway genes and distal colorectal adenoma risk. Int J Colorectal Dis 27, 1587–1595 (2012). https://doi.org/10.1007/s00384-012-1505-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-012-1505-8

Keywords

Search

Navigation