Skip to main content
SpringerLink
Log in

An investigation of the biological basis of an interaction of abdominal fat distribution and family history of breast cancer. A nested study of sisters in the Iowa Women's Health Study (United States)

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

Abstract

Objective: The present study examined whether levels of testosterone, sex hormone binding globulin (SHBG), or insulin levels might underlie an increased risk of postmenopausal breast cancer in women with both high waist-to-hip ratio and a family history of breast cancer disease that was noted earlier in the Iowa Women's Health Study.

Methods: Participants for the current study were selected from 1922 sister groups (3978 women) in the Iowa Women's Health Study cohort. Two groups were included: (1) those with no family history of breast cancer and at least one sister with a high waist-to-hip ratio; or (2) those with a positive family history of breast cancer and at least one sister with a high waist-to-hip ratio. Testosterone, SHBG and insulin were measured by radioimmunoassay from 245 fasting blood samples.

Results: Familial correlations among members of 66 families were estimated at 0.32, 0.28 and 0.25 for serum insulin, free testosterone and SHBG; respectively. Fasting serum insulin was significantly higher in breast cancer family history negative women than in family history positive women, in direct opposition to our a priori hypothesis. No significant differences were observed in serum SHBG or free testosterone across family history categories.

Conclusion: This study corroborates a genetic component to fasting serum insulin, free testosterone and SHBG levels. It seems unlikely that insulin, SHBG, or testosterone explain the interaction between waist-to-hip ratio and family history of breast cancer among participants in the Iowa Women's Health Study.

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

Similar content being viewed by others

References

  1. Kelsey JL, Berkowitz GS (1988) Breast cancer epidemiology. Cancer Res 48: 5615–5623.

    PubMed  Google Scholar 

  2. Ballard-Barbash R, Schatzkin A, Carter CL, et al. (1990) Body fat distrubution and breast cancer in the Framingham Study. J Natl Cancer Inst 82: 286–290.

    PubMed  Google Scholar 

  3. Schapira DV, Kumar NB, Lyman GH, Cox CE (1990) Abdominal obesity and breast cancer risk. Ann Intern Med 112: 182–186.

    PubMed  Google Scholar 

  4. Folsom AR, Kaye SA, Prineas RJ, Potter JP, Gapstur SM, Wallace RB (1990) Increased incidence of carcinoma of the breast associated with abdominal adiposity in postmenopausal women. Am J Epidemiol 131: 794–803.

    PubMed  Google Scholar 

  5. Sellers TA, Kushi LH, Potter JD, et al. (1992) Effect of family history, body-fat distribution, and reproductive factors on the risk of postmenopausal breast cancer. N Engl J Med 326: 1323–1329.

    PubMed  Google Scholar 

  6. Evans DJ, Hoffman RG, Kalkhoff RK, Kissenbah AH (1983) Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. J Clin Endocrinol Metab 57: 304–310.

    PubMed  Google Scholar 

  7. Kirschner MA, Samojlik E, Drejka M, Szmal E, Schneider G, Ertel N (1990) Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab 70: 473–479.

    PubMed  Google Scholar 

  8. Jernström HC, Olsson H, Borg A (1997) Reduced testosterone, 17 beta-oestradiol and sexual hormone binding globulin, and increased insulin-like growth factor-1 concentrations, in healthy nulligravid women aged 19–25 years who were first and/or second degree relatives to breast cancer patients. Eur J Cancer Clin Oncol 6: 330–340.

    Google Scholar 

  9. Secreto G, Toniolo P, Berrino F, et al. (1991) Serum and urinary androgens and risk of breast cancer in postmenopausal women. Cancer Res 51: 2572–2576.

    PubMed  Google Scholar 

  10. Secreto G, Zumo. B (1994) Abnormal production of androgens in women with breast cancer. Anticancer Res 14: 2113–2117.

    PubMed  Google Scholar 

  11. Bernstein L, Ross RK (1993) Endogenous hormones and breast cancer risk. Epidemiol Rev 15: 48–65.

    PubMed  Google Scholar 

  12. Bryan RM, Mercer RJ, Bennett RG, Rennie GC, Lie TH, Morgan FJ (1984) Androgen receptors in breast cancer. Cancer 54: 2436–2440.

    PubMed  Google Scholar 

  13. Soreide JA, Lea OA, Varhaug JE, Skarstein A, Krinnsland S (1992) Androgen receptors in operable breast cancer: relation to other steroid hormone receptors, correlation to prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. Eur J Surg Oncol 13: 112–118.

    Google Scholar 

  14. Henderson BE, Ross RK, Pike MC (1993) Hormonal chemoprevention of cancer in women. Science 259: 633–638.

    PubMed  Google Scholar 

  15. Fortunati N, Raineri M, Cignetti A, Hammond GL, Frairia R (1998) Control of the membrane sex hormone-binding globulin-receptor (SHBG-R) in MCF-7 cells: effect of locally produced SHBG. Steroids 63: 282–284.

    PubMed  Google Scholar 

  16. Selby C (1990) Sex hormone-binding globulin: origin, function, and clinical significance. Ann Clin Biochem 27: 532–541.

    PubMed  Google Scholar 

  17. Moore JW, Key TJA, Clark GMG, Hoare SA, Allen DS, Wang DY (1987) Sex hormone-binding globulin and breast cancer risk. Anticancer Res 7: 1039–1048.

    PubMed  Google Scholar 

  18. Siiteri PK, Hammond GL, Nisker JA (1981) Increased availability of serum estrogens in breast cancer: a new hypothesis. In: Pike MC, Siiteri PK, Welsh CW, eds. Banbury Report 8. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory, pp. 87–101.

    Google Scholar 

  19. O'Brien RM, Granner DK (1996) Regulation of gene expression by insulin. Physiol Rev 76: 1109–1161.

    PubMed  Google Scholar 

  20. Holdaway IM, Friesen HG (1977) Hormone binding by human mammary carcinoma. Cancer Res 37: 1946–1952.

    PubMed  Google Scholar 

  21. Osborne CK, Clemmons DR, Arteaga CI (1990) Regulation of breast cancer growth by insulin-like growth factors. J Steroid Biochem Mol Biol 37: 805–809.

    PubMed  Google Scholar 

  22. Benson EA, Holdaway IM (1982) Regulation of insulin binding to human mammary carcinoma. Cancer Res 42: 1137–1141.

    PubMed  Google Scholar 

  23. Papa V, Pezzino V, Costantino A, et al. (1990) Elevated insulin receptor content in human breast cancer. J Clin Invest 86: 1503–1510.

    PubMed  Google Scholar 

  24. Milazzo G, Giorgino F, Damante G, et al. (1992) Insulin receptor expression and function in human breast cancer cell lines. Cancer Res 52: 3924–3930.

    PubMed  Google Scholar 

  25. Webster NJG, Resnik JL, Reichart DB, Strauss B, Haas M, Seely BL (1996) Repression of the insulin receptor promoter by the tumor suppressor gene product p53: a possible mechanism for receptor overexpression. Cancer Res 56: 2781–2788.

    PubMed  Google Scholar 

  26. Cullen KJ, Yee D, Sly WS, et al. (1990) Insulin-like growth factor receptor expression and function in human breast cancer. Cancer Res 50: 48–53.

    PubMed  Google Scholar 

  27. Mountjoy KG, Finlay GJ, Holdaway IM (1987) Abnormal insulin receptor down regulation and dissociation of down regulation from insulin biological action in cultured human tumor cells. Cancer Res 47: 6500–6504.

    PubMed  Google Scholar 

  28. Bruning PF, Bonfrer JMG, van Noord PAH, Hart AA, de Jong-Bakker M, Nooijen WJ (1992) Insulin resistance and breast cancer risk. Int J Cancer 52: 511–516.

    PubMed  Google Scholar 

  29. Begg L, Kuller LH, Gutai JP, Caggiula AG, Wolmark N, Watson CG (1987) Endogenous sex hormone levels and breast cancer risk. Genet Epidemiol 4: 233–247.

    PubMed  Google Scholar 

  30. Kushi LH, Kaye SA, Folsom AR, Soler JT, Prineas RJ (1988) Accuracy and reliability of self-measurement of body girths. Am J Epidemiol 128: 740–748.

    PubMed  Google Scholar 

  31. SAS Institute Inc. (1989) SAS/STAT User's Guide. Cary, NC: SAS Institute Inc.

    Google Scholar 

  32. SAGE (1994) Statistical Analysis for Genetic Epidemiology. Cleveland, OH: Rammelkamp Center for Education and Research; Case Western Reserve University.

    Google Scholar 

  33. Neter J, Wasserman W, Kutner MH (1985) Applied Linear Statistical Models: regression, analysis of variance, and experimental designs. Homewood, IL: Irwin, pp. 503–504.

    Google Scholar 

  34. Sellers TA, Gapstur SM, Potter JD, Kushi LH, Bostick RM, Folsom AR (1993) Association of body fat distribution and family histories of breast and ovarian cancer with risk of postmenopausal breast cancer. Am J Epidemiol 138: 799–803.

    PubMed  Google Scholar 

  35. ARIC Investigators (1989) Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol 129: 687–702.

    Google Scholar 

  36. 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.

    PubMed  Google Scholar 

  37. Frittitta L, Vigneri R, Papa V, Goldfine ID, Grasso G, Trischitta V (1993) Structural and functional studies of insulin receptors in human breast cancer. Breast Cancer Res Treat 25: 73–82.

    PubMed  Google Scholar 

  38. Papa V, Costantino A, Belfior A (1997) Insulin receptor: what role in breast cancer? Trends Endocrinol Metab 8: 306–312.

    Google Scholar 

  39. Key TJA, Pike MC (1988) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 24: 29–43.

    PubMed  Google Scholar 

  40. Garland CF, Friedlander NJ, Barrett-Connor E, Khaw KT (1992) Sex hormones and postmenopausal breast cancer: a prospective study in an adult community. Am J Epidemiol 135: 1220–1230.

    PubMed  Google Scholar 

  41. Thomas HV, Key TJ, Allen DS, et al. (1997) A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey. Br J Cancer 75: 1075–1079.

    PubMed  Google Scholar 

  42. von Schoultz B, Carlstrom K (1989) On the regulation of sex hormone-binding globulin: a challenge of an old dogma and outlines of an alternative mechanism. J Steroid Biochem 32: 327–334.

    PubMed  Google Scholar 

  43. Kaye SA, Folsom AR, Sprafka JM, Prineas RJ, Wallace RB (1991) Increased incidence of diabetes mellitus in relation to abdominal adiposity in older women. J Clin Epidemiol 44: 329–334.

    PubMed  Google Scholar 

  44. Haarbo J, Marslew U, Gotfredsen A, Christiansen C (1991) Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism 40: 1323–1326.

    PubMed  Google Scholar 

  45. Haffner SM, Katz MS, Stern MP, Dunn JF (1989) Relationship of sex hormone binding globulin to overall adiposity and body fat distribution in a biethnic population. Int J Obes 13: 1–9.

    Google Scholar 

  46. Plymate S, Jones R, Matej J, Friedl K (1988) Regulation of sex hormone-binding globulin in Hep G2 cells by insulin. Steroids 52: 339–340.

    PubMed  Google Scholar 

  47. Stomati M, Hartmann B, Spinetti A, et al. (1996) Effects of hormonal replacement therapy on plasma sex hormone-binding globulin, androgen and insulin-like growth factor-1 levels in postmenopausal women. J Endocrinol Invest 19: 535–541.

    PubMed  Google Scholar 

  48. Edwards KL, Newman B, Mayer E, Selby JV, Krauss RM, Austin MA (1997) Heritability of factors of the insulin resistance syndrome in women twins. Genet Epidemiol 14: 241–253.

    PubMed  Google Scholar 

  49. Narkiewicz K, Chrostowski M, Kuchta G, et al. (1997) Genetic influences on insulinemia in normotensive twins. Am J Hypertens 10: 467–470.

    PubMed  Google Scholar 

  50. Mitchell BD, Kammerer CM, Blangero J, et al. (1996) Genetic and environment contributions to cardiovascular risk factors in Mexican Americans. The San Antonio Family Heart Study. Circulation 94: 2159–2170.

    PubMed  Google Scholar 

  51. Williams RR, Hunt SC, Hopkins PN, et al. (1993) Genetic basis of familial dyslipidemia and hyptertension: 15–year results from Utah. Am J Epidemiol 125: 791–799.

    Google Scholar 

  52. Meikle AW, Bishop DT, Stringham JD, West DW (1987) Quantitating genetic and nongenetic factors that determine plasma sex steroid variation in normal male twins. Metabolism 35: 1090–1095.

    Google Scholar 

  53. Bishop DT, Meikle AW, Slattery ML, Stringham JD, Ford MH, West DW (1988) The effect of nutritional factors on sex hormone levels in male twins. Genet Epidemiol 5: 43–59.

    PubMed  Google Scholar 

  54. Jaquish CE, Blangero J, Haffner SM, Stern MP, MacCluer JW (1997) Quantitative genetics of serum sex hormone-binding globulin levels in participants in the San Antonio Family Heart Study. Metab Clin Exp 46: 988–991.

    PubMed  Google Scholar 

  55. Malkin D, Li FP, Strong LC, et al. (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233–1238.

    Google Scholar 

  56. Miki Y, Swensen J, Shattuck-Eidens D, et al. (1994) A strong candidate gene for the breast and ovarian cancer susceptibility gene, BRCA1. Science 266: 66–71.

    Google Scholar 

  57. Wooster R, Bignell G, Lancaster J, et al. (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378: 789–792.

    PubMed  Google Scholar 

  58. Henderson BE, Feigelson HS (2000) Hormonal carcinogenesis. Carcinogenesis 21: 427–433.

    Article  PubMed  Google Scholar 

  59. Rasmussen AA, Cullen KJ (1998) Paracrine/autocrine regulation of breast cancer by the insulin-like growth factors. Breast Cancer Res Treat 47: 219–233.

    PubMed  Google Scholar 

  60. Oh Y (1998) IGF-independent regulation of breast cancer growth by IGF binding proteins. Breast Cancer Res Treat 47: 283–293.

    PubMed  Google Scholar 

  61. Klein R, Klein BE (1998) Relation of glycemic control to diabetic complications and health outcomes. Diabetes Care 21(Suppl. 3): C39–43.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Health Sciences Research, Mayo Clinic, Rochester, USA

    Janet E. Olson & James R. Cerhan

  2. Mayo Clinic Cancer Center, Mayo Clinic, Rochester, USA

    Janet E. Olson, James R. Cerhan & Thomas A. Sellers

  3. Division of Epidemiology, University of Minnesota, USA

    Kristen E. Anderson & Aaron R. Follsom

Authors
  1. Janet E. Olson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristen E. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James R. Cerhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aaron R. Follsom
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas A. Sellers
    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

Olson, J.E., Anderson, K.E., Cerhan, J.R. et al. An investigation of the biological basis of an interaction of abdominal fat distribution and family history of breast cancer. A nested study of sisters in the Iowa Women's Health Study (United States). Cancer Causes Control 11, 941–954 (2000). https://doi.org/10.1023/A:1026537819055

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026537819055

Search

Navigation