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ESR1, AR, body size, and breast cancer risk in Hispanic and non-Hispanic white women living in the Southwestern United States

  • Epidemiology
  • Published:
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Abstract

Estrogen and androgen are thought to influence breast cancer risk. The actions of estrogens and androgens are mediated through the respective receptors. In this study we examine the association of the Xb1 polymorphism of estrogen receptor alpha (ESR1) and the CAG repeat of the androgen receptor (AR) gene with risk of breast cancer in women living in the Southwestern United States. Cases (N = 1169 non-Hispanic white (NHW) and 576 Hispanic) with first primary breast cancer were matched to controls (N = 1330 NHW and 725 Hispanic) by location (Arizona, Colorado, New Mexico, or Utah) and 5-year age group. Detailed weight history was obtained along with other diet and lifestyle information. Neither the ESR1 nor the AR polymorphisms evaluated were associated independently with breast cancer risk in either Hispanic or NHW women. However, among Hispanic women taking hormone replacement therapy (HRT), there was a 40% reduced risk of breast cancer among women with an X allele (95% CI 0.39, 0.94). Also Hispanic women with the xx genotype had a significant reduced risk of breast cancer in the presence of weight gain prior to age 50 if post-menopausal or prior to diagnosis if pre-menopausal (P interaction 0.02 and <0.01 respectively). These results suggest differences in risk factors for NHW and Hispanic women. However, they provide only minor support for the role of the AR and ESR1 gene in the etiology of breast cancer.

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References

  1. Key T, Appleby P, Barnes I, Reeves G (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94(8):606–616

    PubMed  CAS  Google Scholar 

  2. 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 

  3. Colditz GA (2005) Estrogen, estrogen plus progestin therapy, and risk of breast cancer. Clin Cancer Res 11(2 Pt 2):909s–917s

    PubMed  CAS  Google Scholar 

  4. Pearce ST, Jordan VC (2004) The biological role of estrogen receptors alpha and beta in cancer. Crit Rev Oncol Hematol 50(1):3–22

    Article  PubMed  Google Scholar 

  5. Hackenberg R, Schulz K (1996) Androgen receptor mediated growth control of breast cancer and endometrial cancer modulated by antiandrogen- and androgen-like steroids. J Steroid Biochem Mol Biol 56(1–6 Spec No):113–117

    Article  PubMed  CAS  Google Scholar 

  6. Riva C, Dainese E, Caprara G, Rocca PC, Massarelli G, Tot T, Capella C, Eusebi V (2005) Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma. Virchows Arch 447(4):695–700

    Article  PubMed  CAS  Google Scholar 

  7. Latil AG, Azzouzi R, Cancel GS, Guillaume EC, Cochan-Priollet B, Berthon PL, Cussenot O (2001) Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways. Cancer 92(5):1130–1137

    Article  PubMed  CAS  Google Scholar 

  8. Katzenellenbogen BS, Montano MM, Ediger TR, Sun J, Ekena K, Lazennec G, Martini PG, McInerney EM, Delage-Mourroux R, Weis K, Katzenellenbogen JA (2000) Estrogen receptors: selective ligands, partners, and distinctive pharmacology. Recent Prog Horm Res 55:163–193 (discussion 194–195)

    PubMed  CAS  Google Scholar 

  9. Katzenellenbogen BS, Choi I, Delage-Mourroux R, Ediger TR, Martini PG, Montano M, Sun J, Weis K, Katzenellenbogen JA (2000) Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology. J Steroid Biochem Mol Biol 74(5):279–285

    Article  PubMed  CAS  Google Scholar 

  10. Balfe P, McCann A, McGoldrick A, McAllister K, Kennedy M, Dervan P, Kerin MJ (2004) Estrogen receptor alpha and beta profiling in human breast cancer. Eur J Surg Oncol 30(5):469–474

    Article  PubMed  CAS  Google Scholar 

  11. Ali S, Coombes RC (2000) Estrogen receptor alpha in human breast cancer: occurrence and significance. J Mammary Gland Biol Neoplasia 5(3):271–281

    Article  PubMed  CAS  Google Scholar 

  12. Becherini L, Gennari L, Masi L, Mansani R, Massart F, Morelli A, Falchetti A, Gonnelli S, Fiorelli G, Tanini A, Brandi ML (2000) Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in post-menopausal Italian women. Hum Mol Genet 9(13):2043–2050

    Article  PubMed  CAS  Google Scholar 

  13. van Meurs JB, Schuit SC, Weel AE, van der Klift M, Bergink AP, Arp PP, Colin EM, Fang Y, Hofman A, van Duijn CM, van Leeuwen JP, Pols HA, Uitterlinden AG (2003) Association of 5′ estrogen receptor alpha gene polymorphisms with bone mineral density, vertebral bone area and fracture risk. Hum Mol Genet 12(14):1745–1754

    Article  PubMed  CAS  Google Scholar 

  14. Gennari L, Merlotti D, De Paola V, Calabro A, Becherini L, Martini G, Nuti R (2005) Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol 161(4):307–320

    Article  PubMed  CAS  Google Scholar 

  15. Onland-Moret NC, van Gils CH, Roest M, Grobbee DE, Peeters PH (2005) The estrogen receptor alpha gene and breast cancer risk (The Netherlands). Cancer Causes Control 16(10):1195–1202

    Article  PubMed  Google Scholar 

  16. Modugno F, Zmuda JM, Potter D, Cai C, Ziv E, Cummings SR, Stone KL, Morin PA, Greene D, Cauley JA (2005) Association of estrogen receptor alpha polymorphisms with breast cancer risk in older Caucasian women. Int J Cancer 116(6):984–991

    Article  PubMed  CAS  Google Scholar 

  17. Boyapati SM, Shu XO, Ruan ZX, Cai Q, Smith JR, Wen W, Gao YT, Zheng W (2005) Polymorphisms in ER-alpha gene interact with estrogen receptor status in breast cancer survival. Clin Cancer Res 11(3):1093–1098

    PubMed  CAS  Google Scholar 

  18. Gold B, Kalush F, Bergeron J, Scott K, Mitra N, Wilson K, Ellis N, Huang H, Chen M, Lippert R, Halldorsson BV, Woodworth B, White T, Clark AG, Parl FF, Broder S, Dean M, Offit K (2004) Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Cancer Res 64(24):8891–8900

    Article  PubMed  CAS  Google Scholar 

  19. Kirkegaard T, Witton CJ, McGlynn LM, Tovey SM, Dunne B, Lyon A, Bartlett JM (2005) AKT activation predicts outcome in breast cancer patients treated with tamoxifen. J Pathol 207(2):139–146

    Article  PubMed  CAS  Google Scholar 

  20. Salamone LM, Glynn NW, Black DM, Ferrell RE, Palermo L, Epstein RS, Kuller LH, Cauley JA (1996) Determinants of premenopausal bone mineral density: the interplay of genetic and lifestyle factors. J Bone Miner Res 11(10):1557–1565

    Article  PubMed  CAS  Google Scholar 

  21. Ding D, Xu L, Menon M, Reddy GP, Barrack ER (2004) Effect of a short CAG (glutamine) repeat on human androgen receptor function. Prostate 58(1):23–32

    Article  PubMed  CAS  Google Scholar 

  22. Krithivas K, Yurgalevitch SM, Mohr BA, Wilcox CJ, Batter SJ, Brown M, Longcope C, McKinlay JB, Kantoff PW (1999) Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men. J Endocrino l162(1):137–142

    Article  Google Scholar 

  23. Westberg L, Baghaei F, Rosmond R, Hellstrand M, Landen M, Jansson M, Holm G, Bjorntorp P, Eriksson E (2001) Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women. J Clin Endocrinol Metab 86(6):2562–2568

    Article  PubMed  CAS  Google Scholar 

  24. WHO (2002) Weight control and physical activity. IARC handbooks of cancer prevention. vol. 6. Lyon, France: IARC Press

    Google Scholar 

  25. Howard CA, Samet JM, Buechley RW, Schrag SD, Key CR (1983) Survey research in New Mexico Hispanics: some methodological issues. Am J Epidemiol 117(1):27–34

    PubMed  CAS  Google Scholar 

  26. Edwards S, Slattery ML, Mori M, Berry TD, Caan BJ, Palmer P, Potter JD (1994) Objective system for interviewer performance evaluation for use in epidemiologic studies. Am J Epidemiol 140(11):1020–1028

    PubMed  CAS  Google Scholar 

  27. Sweeney C, Wolff RK, Byers T, Baumgartner KB, Guiliano AR, Herrick JS, Murtaugh MA, Samowitz WS, Slattery ML (2006) Genetic admixture and candidate genes among Hispanics: potential for confounding in a breast cancer study? Cancer Epidemiol Biomarkers Prev (in press)

  28. Hosmer DW, Lemeshow S (1992) Confidence interval estimation of interaction. Epidemiology 3(5):452–456

    Article  PubMed  CAS  Google Scholar 

  29. Tutton PJ, Barkla DH (1988) Steroid hormones as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review). Anticancer Res 8(3):451–456

    PubMed  CAS  Google Scholar 

  30. Weel AE, Uitterlinden AG, Westendorp IC, Burger H, Schuit SC, Hofman A, Helmerhorst TJ, van Leeuwen JP, Pols HA (1999) Estrogen receptor polymorphism predicts the onset of natural and surgical menopause. J Clin Endocrinol Metab 84(9):3146–3150

    Article  PubMed  CAS  Google Scholar 

  31. Lorentzon M, Lorentzon R, Backstrom T, Nordstrom P (1999) Estrogen receptor gene polymorphism, but not estradiol levels, is related to bone density in healthy adolescent boys: a cross-sectional and longitudinal study. J Clin Endocrinol Metab 84(12):4597–4601

    Article  PubMed  CAS  Google Scholar 

  32. Khosla S, Riggs BL, Atkinson EJ, Oberg AL, Mavilia C, Del Monte F, Melton LJ 3rd, Brandi ML (2004) Relationship of estrogen receptor genotypes to bone mineral density and to rates of bone loss in men. J Clin Endocrinol Metab 89(4):1808–1816

    Article  PubMed  CAS  Google Scholar 

  33. Schuit SC, de Jong FH, Stolk L, Koek WN, van Meurs JB, Schoofs MW, Zillikens MC, Hofman A, van Leeuwen JP, Pols HA, Uitterlinden AG (2005) Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in post-menopausal women. Eur J Endocrinol 153(2):327–334

    Article  PubMed  CAS  Google Scholar 

  34. Ferro P, Catalano MG, Raineri M, Reato G, dell’Eva R, Risio M, Foa R, Fortunati N, Pfeffer U (2000) Somatic alterations of the androgen receptor CAG repeat in human colon cancer delineate a novel mutation pathway independent of microsatellite instability. Cancer Genet Cytogenet 123(1):35–40

    Article  PubMed  CAS  Google Scholar 

  35. Mulholland DJ, Cheng H, Reid K, Rennie PS, Nelson CC (2002) The androgen receptor can promote beta-catenin nuclear translocation independently of adenomatous polyposis coli. J Biol Chem 277(20):17933–17943

    Article  PubMed  CAS  Google Scholar 

  36. Modugno F, Weissfeld JL, Trump DL, Zmuda JM, Shea P, Cauley JA, Ferrell RE (2001) Allelic variants of aromatase and the androgen and estrogen receptors: toward a multigenic model of prostate cancer risk. Clin Cancer Res 7(10):3092–3096

    PubMed  CAS  Google Scholar 

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Acknowledgements

This study was funded by grants: CA 078682, CA 078762, CA 078552, CA 078802. This research also was supported by the Utah Cancer Registry, which is funded by Contract #N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the New Mexico Tumor Registry, funded by contract #, and the Arizona and Colorado cancer registries, funded by the Centers for Disease Control and Prevention National Program of Cancer Registries and additional state support. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute. We would like to acknowledge the contributions of Sandra Edwards, Roger Edwards, Leslie Palmer, Betsy Riesendal, Karen Curtin, Tara Patton, Jason Witter, and Kelly May to this study.

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Author notes

  1. Kathy Baumgartner

    Present address: University of Louisville, Louisville, KY, USA

  2. Anna Giuliano

    Present address: Moffitt Cancer Center, Tampa, FL, USA

Authors and Affiliations

  1. Health Research Center, University of Utah, Salt Lake City, Utah, 84117, USA

    Martha L. Slattery, Carol Sweeney, Jennifer Herrick & Roger Wolff

  2. Department of Internal Medicine and the Cancer Research and Treatment Center Epidemiology and Cancer Prevention Program, University of New Mexico Health Science Center, Albuquerque, NM, USA

    Kathy Baumgartner

  3. University of Arizona, Tucson, AZ, USA

    Anna Giuliano

  4. University of Colorado School of Medicine, Denver, CO, USA

    Tim Byers

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  1. Martha L. Slattery
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Correspondence to Martha L. Slattery.

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Slattery, M.L., Sweeney, C., Herrick, J. et al. ESR1, AR, body size, and breast cancer risk in Hispanic and non-Hispanic white women living in the Southwestern United States. Breast Cancer Res Treat 105, 327–335 (2007). https://doi.org/10.1007/s10549-006-9453-z

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  • DOI: https://doi.org/10.1007/s10549-006-9453-z

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