Skip to main content
SpringerLink
Log in

Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States)

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

Abstract

Objective: The association between body mass index (BMI) and colon cancer has been reported to be different for men and women. No prior literature has examined if estrogen influences these differences. Methods: Using data from an incident population-based case (n = 1972) and control (n = 2386) study of colon cancer we evaluated if estrogen modifies the association between BMI and risk of colon cancer. Results: Women who were estrogen-negative (postmenopausal women not taking hormone replacement therapy, HRT) were at increased risk of colon cancer regardless of indicator of estrogen status used (i.e. estrogen-negative compared to estrogen-positive women defined as either being premenopausal or postmenopausal women using HRT, OR 1.54, 95% CI 1.23–1.93; no recent exposure to estrogens compared to current or HRT use within the past 2 years, OR 1.58, 95% CI 1.24–2.00; postmenopausal women not currently using HRT compared to postmenopausal women taking HRT, OR 1.65, 95% CI 1.29–2.12). BMI (kg/m2) was not associated with an increased risk of colon cancer among women who were estrogen-negative. However, women who were estrogen-positive experienced a greater than two-fold increase in colon cancer risk if they had a BMI of > 30 relative to those who had a BMI of <23 (for estrogen-positive, OR, 2.50, 95% CI 1.51–4.13; premenopausal, OR 2.19, 95% CI 0.94–5.07; postmenopausal using HRT, OR 3.36, 95% CI 1.58–7.13). Among men the colon cancer risk associated with BMI decreased with advancing age. Physical activity modified the increased colon cancer risk associated with a large BMI. Conclusions: These data suggest the importance of estrogen in colon cancer etiology. Being estrogen-negative resulted in a significant increased risk of colon cancer. However, BMI significantly increased the risk of colon cancer among women who were estrogen-positive. We hypothesize that estrogen up-regulates IGF-I receptors and IRS-I levels in the colon, which in turn increases susceptibility to obesity-induced increased levels of insulin. We further hypothesize that androgens may have similar effects in men given the decline in colon cancer risk associated with BMI with advancing age.

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.

Similar content being viewed by others

References

  1. Alley PG,McNee RK (1986) Age and sex differences in right colon cancer. Dis Colon Rectum 29: 227-229.

    Google Scholar 

  2. Potter JD,Slattery ML,Bostick RM,Gasptur SM (1993) Colon cancer: a review of the epidemiology. Epidemiol Rev 15: 499-545.

    Google Scholar 

  3. Hebert-Croteau N (1998) A meta-analysis of hormone replacement therapy and colon cancer in women. Cancer Epidemiol Biomarkers Prev 7: 653-659.

    Google Scholar 

  4. Potter JD (1995) Hormones and colon cancer. J Natl Cancer Inst 87: 1039-1040.

    Google Scholar 

  5. Breivik J,Lothe RA,Meling GI,Rognum TO,Borresen-Dale AL,Gaudernack G (1997) Different genetic pathways to proximal and distal colorectal cancer influenced by sex-related factors. Int J Cancer 74: 664-669.

    Google Scholar 

  6. McMichael JA,Potter JD (1980) Reproduction, endogenous and exogenous sex hormones, and colon cancer: a review and hypothesis. J Natl Cancer Inst 65: 1201-1207.

    Google Scholar 

  7. Potter JD,McMichael AJ (1983) Large bowel cancer in relation to reproductive and hormonal factors: a case-control study. J Natl Cancer Inst 71: 703-709.

    Google Scholar 

  8. Caan BJ,Coates AO,Slattery ML,Potter JD,Quesenberry CP Jr,Edwards S (1998) Body size and colon cancer in a large case-control study. Int J Obesity Relat Metab Disord 22: 178-184.

    Google Scholar 

  9. Murphy TK,Calle EE,Rodriguez C,Khan HS,Thun MJ (2000) Body mass index and colon cancer mortality in a large prospective study. Am J Epidemiol 152: 847-854.

    Google Scholar 

  10. International Agency for Research on Cancer(2002) Body Size and Colon Cancer. Lyon: IARC.

    Google Scholar 

  11. Dupont J,Karas M,LeRoith D (2000) The potentiation of estrogen on insulin-like growth factor I action in MCF-7 human breast cancer cells includes cell cycle components. J Biol Chem 275: 35893-35901.

    Google Scholar 

  12. Lee AV,Jackson JG,Gooch JL, et al. (1999) Enhancement of insulin-like growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrat-1 expression in vitro and in vivo. Mol Endocrinol 13: 787-796.

    Google Scholar 

  13. Stewart AJ,Johnson MD,Mat FE,Westley BR (1990) Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. J Biol Chem 265: 321172-321178.

    Google Scholar 

  14. Kampman E,Potter JD,Slattery ML,Edwards S,Caan BJ (1997) Hormone replacement therapy, reproductive history, and colon cancer: a US multi-center case-control study. Cancer Causes Control 8: 146-158.

    Google Scholar 

  15. Newcomb PA,Storer BE (1995) Postmenopausal hormone use and risk of large-bowel cancer. J Natl Cancer Inst 87: 1067-1071.

    Google Scholar 

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

    Google Scholar 

  17. Ma P,Pollak MN,Giovannucci E, et al. (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.

    Google Scholar 

  18. McKeown-Eyssen G (1994) Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev 3: 687-696.

    Google Scholar 

  19. Slattery ML,Potter JD,Caan BJ, et al. (1997) Energy balance and colon cancer: beyond physical activity. Cancer Res 57: 75-80.

    Google Scholar 

  20. Edwards S,Slattery ML,Mori M,Berry TD,Palmer P (1994) Objective system for interviewer performance evaluation for use in epidemiologic studies. Am J Epidemiol 140: 1020-1028.

    Google Scholar 

  21. Slattery ML,Caan B,Duncan D. et al. (1994) A computerized diet history questionnaire for epidemiologic studies. J Am Diet Assoc 94: 761-766.

    Google Scholar 

  22. Slattery ML,Edwards SL,Ma KN,Friedman FG,Potter JD (1997) Physical activity and colon cancer: a public health perspective. Ann Epidemiol 7: 137-145.

    Google Scholar 

  23. Rodriquez C,Calle EE,Patel AV,Tatham LM,Jacobs EJ,Thun MJ (2001) Effect of body mass on the association between estrogen replacement and mortality among elderly US women. Am J Epidemiol 153: 145-152.

    Google Scholar 

  24. Huang Z,Hankinson SE,Colditz GA, et al. (1997) Dual effects of weight and weight gain on breast cancer risk. JAMA 278: 1407-1411.

    Google Scholar 

  25. Harris RE,Namboodiri KK,Wynder EL (1992) Breast cancer risk: effects of estrogen replacement therapy and body mass. J Natl Caner Inst 84: 1575-1582.

    Google Scholar 

  26. Chu SY,Lee NC,Wingo PA,Senie RT,Greenberg RS,Peterson HB (1991) The relationship between body mass and breast cancer among women enrolled in the Cancer and Steroid Hormone Study. J Clin Epidemiol 11: 1197-1206.

    Google Scholar 

  27. Kuper H,Cramer DW,Tiktus-Ernstoff L (2002) Risk of ovarian cancer in the United States in relation to anthropometric measures: does the association depend on menopausal status? Cancer Causes Control 13: 455-463.

    Google Scholar 

  28. Women's Health Initiative Investigator's Group(2002) Risks and benefits of estrogen plus progestin in health post-menopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 288: 321-333.

    Google Scholar 

  29. Lipworth L,Adami H-O,Trichopoulos D,Carlstrom K,Mantzoros C (1996) Serum steroid hormone levels, sex hormone-binding globulin, and body mass index in the etiology of postmenopausal breast cancer. Epidemiology 7: 96-100.

    Google Scholar 

  30. Krauss RM,Burkman RT Jr (1992) The metabolic impact of oral contraceptives. Am J Obstet Gynecol 167: 1177-1184.

    Google Scholar 

  31. Polderman KH,Gooren LJ,Asscheman H,Bakker A,Heine RJ (1994) Induction of insulin resistance by androgens and estrogens. J Clin Endocrinol Metab 79: 265-271.

    Google Scholar 

  32. Goldfine ID,Papa V,Vigneri R,Siiteri P,Rosenthal S (1992) Progestin regulation of insulin and insulin-like growth factor I receptors in cultured human breast cancer cells. Breast Cancer Res Treat 22: 69-79.

    Google Scholar 

  33. Katzenellenbogen BS,Norman MJ (1990) Multihormonal regulation of the progesterone receptor in MCF-7 human breast cancer cells: interrelationships among insulin/insulin-like growth factor-I, serum, and estrogen. Endocrinology 126: 891-898.

    Google Scholar 

  34. Slattery ML,Potter JD,Curtin K, et al. (2001) Estrogens reduce and withdrawal of estrogens increases risk of microsatellite instability-positive colon cancer. Cancer Res 61: 126-130.

    Google Scholar 

  35. Kadowaki T,Tobe K,Honda-Yamamoto R, et al. (1996) Signal transduction mechanism of insulin and insulin-like growth factor-1. Endocrinol J 43: S33-S41.

    Google Scholar 

  36. Werner H,LeRoith D (1996) The role of the insulin-like growth factor system in human cancer. Adv Cancer Res 68: 183-223.

    Google Scholar 

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

    Google Scholar 

  38. Giovannucci E,Pollak MN,Platz EA, et al. (2000) Plasma insulinlike growth factor-1 and binding protein-3 and risk of colorectal cancer and adenoma in women. Cancer Epidemiol Biomarkers Prev 9: 345-349.

    Google Scholar 

  39. Molloy CA.May FEB,Westley BR (2000) Insulin receptor substrate-1 expression is regulated by estrogen in the MCF-7 human breast cancer cell line. J Biol Chem 275: 12565-12571.

    Google Scholar 

  40. Lee AV,Jackson JG,Gooch JL, et al. (1999) Enhancement of insulin-like growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo. Mol Endocrinol 13: 787-796.

    Google Scholar 

  41. McCarty MF (1997) Up-regulation of IGF binding protein-1 as an anticarcinogenic strategy: relevance to caloric restriction, exercise, and insulin sensitivity. Med Hypoth 48: 297-308.

    Google Scholar 

  42. Kopelman PG (1994) Hormones and obesity. Bailliere's Clin Endocrinol Metab 8: 549-575.

    Google Scholar 

  43. Butler AA,Yakar S,Gewolb IH,Karas M,Okubo Y,LeRoith D (1998) Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology. Comp Biochem Physiol 121: 19-26.

    Google Scholar 

  44. Butler AA,Blakesley VA,Poulaki V, et al. (1998) Stimulation of tumor growth by recombinant human insulin-like growth factor-I (IGF-I) is dependent on the dose and the level of IGF-I receptor expression. Cancer Res 58: 3021-3027.

    Google Scholar 

  45. Sachdev D,Yee D (2001) The IGF system and breast cancer. Endocr-Rel Cancer 8: 197-209.

    Google Scholar 

  46. 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.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Health Research Center, Department of family and Preventive Medicine, University of Utah, 375 Chipeta Way, Suite A, Salt Lake City, UT, 84108, USA

    M.L. Slattery & Sandra Edwards

  2. National Cancer Institute, Oakland, CA, USA

    Rachel Ballard-Barbash

  3. Kaiser Permanente Medical Care Program, Oakland, CA, USA

    Bette J. Caan

  4. Fred Hutchinson Cancer Research Center, Seattle, Washington, DC, USA

    John D. Potter

Authors
  1. M.L. Slattery
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel Ballard-Barbash
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandra Edwards
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bette J. Caan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John D. Potter
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slattery, M., Ballard-Barbash, R., Edwards, S. et al. Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States). Cancer Causes Control 14, 75–84 (2003). https://doi.org/10.1023/A:1022545017867

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022545017867

Search

Navigation