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An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors

  • Epidemiology
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Abstract

Insulin receptor substrate-1 (IRS-1) is a key downstream signaling molecule common to both the insulin and IGF signaling pathways that can interact with the estrogen pathway to regulate breast cell growth. We investigated whether a putative functional variant for IRS-1 (G972R) influences circulating levels of sex hormones, sex hormone binding globulin (SHBG), C-peptide, and insulin-like growth factor 1 (IGF-1) levels among post-menopausal African-American and non-Hispanic white breast cancer patients enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. Circulating levels of sex hormones and growth factors can influence breast cancer recurrence and survival. Serum estrone, estradiol, testosterone, SHBG, IGF-1 and C-peptide were measured in 468 patients at 30+ months post diagnosis. Non-protein bound hormone levels (free estradiol, free testosterone) were calculated. In African-American patients, the IRS-1 variant was associated with increased serum levels of estrone (p=0.02), free estradiol (p=0.04), total testosterone (p=0.04), free testosterone (p=0.006) and decreased levels of sex hormone-binding globulin (p=0.02). No association was present for white patients. Our findings provide suggestive evidence that IRS-1 G972R variant may be associated with circulating levels of sex hormones and SHBG in African American breast cancer survivors.

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Abbreviations

CV:

Coefficient of variation

E2 :

Estradiol

E1 :

Estrone

ER:

Estrogen receptor

HEAL:

Health, Eating, Activity, and Lifestyle Study

HT:

Hormone replacement therapy

IRS-1:

Insulin receptor substrate-1

IGF-1:

Insulin-like growth factor 1

IGF1R:

Insulin-like growth factor 1 receptor

IGFBPs:

IGF binding proteins

SHBG:

Sex hormone binding globulin

T:

Testosterone

G972R:

Amino acid change (glycine to arginine) at codon 972

References

  1. Persson I (2000) Estrogens in the causation of breast, endometrial and ovaria0n cancers – evidence and hypotheses from epidemiological findings. J Steroid Biochem Mol Biol 74(5):357–364

    Article  PubMed  CAS  Google Scholar 

  2. Lonning PE, Helle SI, Johannessen DC, Ekse D, Adlercreutz H (1996) Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer. Breast Cancer Res Treat 39(3):335–341

    Article  PubMed  CAS  Google Scholar 

  3. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy (1992) 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Early Breast Cancer Trialists’ Collaborative Group. Lancet 339(8784):1–15

    Google Scholar 

  4. Tamoxifen for early breast cancer: an overview of the randomised trials (1998) Early Breast Cancer Trialists’ Collaborative Group. Lancet 351(9114):1451–1467

  5. Baum M, Buzdar A, Cuzick J, Forbes J, Houghton J, Howell A, Sahmoud T (2003) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 98(9):1802–1810

    Article  PubMed  CAS  Google Scholar 

  6. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, et al (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350(11):1081–1092

    Article  PubMed  CAS  Google Scholar 

  7. Hamelers IH, Steenbergh PH (2003) Interactions between estrogen and insulin-like growth factor signaling pathways in human breast tumor cells. Endocr Relat Cancer 10(2):331–345

    Article  PubMed  CAS  Google Scholar 

  8. Yee D (1994) The insulin-like growth factor system as a target in breast cancer. Breast Cancer Res Treat 32(1):85–95

    Article  PubMed  CAS  Google Scholar 

  9. Lee AV, Hilsenbeck SG, Yee D (1998) IGF system components as prognostic markers in breast cancer. Breast Cancer Res Treat 47(3):295–302

    Article  PubMed  CAS  Google Scholar 

  10. Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, Hartwick W, Hoffman B, Hood N (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51

    Article  PubMed  CAS  Google Scholar 

  11. Lee AV, Jackson JG, Gooch JL, Hilsenbeck SG, Coronado-Heinsohn E, Osborne CK, Yee D (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(5):787–796

    Article  PubMed  CAS  Google Scholar 

  12. Ando S, Panno ML, Salerno M, Sisci D, Mauro L, Lanzino M, Surmacz E (1998) Role of IRS-1 signaling in insulin-induced modulation of estrogen receptors in breast cancer cells. Biochem Biophys Res Commun 253(2):315–319

    Article  PubMed  CAS  Google Scholar 

  13. Freiss G, Puech C, Vignon F (1998) Extinction of Insulin-like growth factor-i mitogenic signaling by antiestrogen-stimulated Fas-associated protein tyrosine phosphatase-1 in human breast cancer cells. Mol Endocrinol 12(4):568–579

    Article  PubMed  CAS  Google Scholar 

  14. Stewart A, Johnson M, May F, Westley B (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(34):21172–21178

    PubMed  CAS  Google Scholar 

  15. Huynh H, Nickerson T, Pollak M, Yang X (1996) Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI 182780. Clin Cancer Res 2(12):2037–2042

    PubMed  CAS  Google Scholar 

  16. 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(17):12565–12571

    Article  PubMed  CAS  Google Scholar 

  17. Perks C, Holly J (2000) Insulin-like growth factor binding proteins (IGFBPs) in breast cancer. J Mammary Gland Biol Neoplasia 5(1):75–84

    Article  PubMed  CAS  Google Scholar 

  18. Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H (2001) Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha . A new model for anti-estrogen resistance. J Biol Chem 276(13):9817–9824

    Article  PubMed  CAS  Google Scholar 

  19. Endoh H, Maruyama K, Masuhiro Y, Kobayashi Y, Goto M, Tai H, Yanagisawa J, Metzger D, Hashimoto S, Kato S (1999) Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha. Mol Cell Biol 19(8):5363–5372

    PubMed  CAS  Google Scholar 

  20. Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, et al (1995) Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270(5241): 1491–1494

    Article  PubMed  CAS  Google Scholar 

  21. Dufourny B, Alblas J, van Teeffelen HAAM, van Schaik FMA, van der Burg B, Steenbergh PH, Sussenbach JS (1997) Mitogenic signaling of insulin-like growth factor I in MCF-7 human breast cancer cells requires phosphatidylinositol 3-kinase and is independent of mitogen-activated protein kinase. J Biol Chem 272(49):31163–31171

    Article  PubMed  CAS  Google Scholar 

  22. Bezerra RMN, de Castro V, Sales T, Passini R Jr, Marba STM, Saad STO, Saad MJA (2002) The Gly972Arg polymorphism in insulin receptor substrate-1 is associated with decreased birth weight in a population-based sample of Brazilian newborns. Diabetes Care 25(3):550–553

    Article  PubMed  CAS  Google Scholar 

  23. Jackson JG, White MF, Yee D (1998) Insulin receptor substrate-1 is the predominant signaling molecule activated by insulin-like growth factor-I, insulin, and interleukin-4 in estrogen receptor-positive human breast cancer cells. J Biol Chem 273(16):9994–10003

    Article  PubMed  CAS  Google Scholar 

  24. Sesti G, Federici M, Hribal ML, Lauro D, Sbraccia P, Lauro R (2001) Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. Faseb J 15(12):2099–2111

    Article  PubMed  CAS  Google Scholar 

  25. Almind K, Inoue G, Pedersen O, Kahn CR (1996) A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies. J␣Clin Invest 97(11):2569–2575

    Article  PubMed  CAS  Google Scholar 

  26. Clausen JO, Hansen T, Bjorbaek C, Echwald SM, Urhammer SA, Rasmussen S, Andersen CB, Hansen L, Almind K, Winther K, et al (1995) Insulin resistance: interactions between obesity and a common variant of insulin receptor substrate-1. Lancet 346(8972):397–402

    Article  PubMed  CAS  Google Scholar 

  27. Baroni MG, Arca M, Sentinelli F, Buzzetti R, Capici F, Lovari S, Vitale M, Romeo S, Di Mario U (2001) The G972R variant of the insulin receptor substrate-1 (IRS-1) gene, body fat distribution and insulin-resistance. Diabetologia 44(3):367–372

    Article  PubMed  CAS  Google Scholar 

  28. Almind K, Bjorbaek C, Vestergaard H, Hansen T, Echwald S, Pedersen O (1993) Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Lancet 342(8875):828–832

    Article  PubMed  CAS  Google Scholar 

  29. Jellema A, Zeegers MP, Feskens EJ, Dagnelie PC, Mensink RP (2003) Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies. Diabetologia 46(7):990–995

    Article  PubMed  CAS  Google Scholar 

  30. Baroni MG, D’Andrea MP, Montali A, Pannitteri G, Barilla F, Campagna F, Mazzei E, Lovari S, Seccareccia F, Campa PP, et al (1999) A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol 19(12):2975–2980

    PubMed  CAS  Google Scholar 

  31. Holzl B, Iglseder B, Stadlmayr A, Hedegger M, More E, Reiter R, Sandhofer F, Paulweber B (2003) Intima media thickness of carotid arteries is reduced in heterozygous carriers of the Gly972Arg variant in the insulin receptor substrate-1 gene. Eur J Clin Invest 33(2):110–116

    Article  PubMed  CAS  Google Scholar 

  32. Porzio O, Federici M, Hribal ML, Lauro D, Accili D, Lauro R, Borboni P, Sesti G (1999) The Gly972–>Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic beta cells. J Clin Invest 104(3):357–364

    Article  PubMed  CAS  Google Scholar 

  33. McTiernan A, Rajan KB, Tworoger SS, Irwin M, Bernstein L, Baumgartner R, Gilliland F, Stanczyk FZ, Yasui Y, Ballard-Barbash R (2003) Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol 21(10):1961–1966

    Article  PubMed  CAS  Google Scholar 

  34. Tsai C-T, Hwang J-J, Lai L-P, Chiang F-T, Tseng Y-Z (2002) IRS-1 Gly971Arg variant is not a new risk factor for coronary artery disease in the Taiwanese population. Arterioscler Thromb Vasc Biol 22(1):194

    PubMed  CAS  Google Scholar 

  35. Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J␣Steroid Biochem 16(6):801–810

    Article  PubMed  CAS  Google Scholar 

  36. Falk RT, Dorgan JF, Kahle L, Potischman N, Longcope C (1997) Assay reproducibility of hormone measurements in postmenopausal women. Cancer Epidemiol Biomarkers Prev 6(6):429–432

    PubMed  CAS  Google Scholar 

  37. McShane LM, Dorgan JF, Greenhut S, Damato JJ (1996) Reliability and validity of serum sex hormone measurements. Cancer Epidemiol Biomarkers Prev 5(11):923–928

    PubMed  CAS  Google Scholar 

  38. Livak KJ (1999) Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal 14(5–6):143–149

    PubMed  CAS  Google Scholar 

  39. Ogden CL, Flegal KM, Carroll MD, Johnson CL (2002) Prevalence and trends in overweight among US children and adolescents, 1999–2000. JAMA 288(14):1728–1732

    Article  PubMed  Google Scholar 

  40. El Mkadem SA, Lautier C, Macari F, Molinari N, Lefebvre P, Renard E, Gris JC, Cros G, Daures JP, Bringer J, et al (2001) Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome. Diabetes 50(9):2164–2168

    Article  PubMed  CAS  Google Scholar 

  41. Weiss SE, Tartter PI, Ahmed S, Brower ST, Brusco C, Bossolt K, Amberson JB, Bratton J (1995) Ethnic differences in risk and prognostic factors for breast cancer. Cancer 76(2):268–274

    Article  PubMed  CAS  Google Scholar 

  42. O’Malley CD, Le GM, Glaser SL, Shema SJ, West DW (2003) Socioeconomic status and breast carcinoma survival in four racial/ethnic groups: a population-based study. Cancer 97(5):1303–1311

    Article  PubMed  Google Scholar 

  43. Simon MS, Severson RK (1996) Racial differences in survival of female breast cancer in the Detroit metropolitan area. Cancer 77(2):308–314

    Article  PubMed  CAS  Google Scholar 

  44. Natarajan N, Nemoto T, Mettlin C, Murphy GP (1985) Race-related differences in breast cancer patients. Results of the 1982 national survey of breast cancer by the American College of Surgeons. Cancer 56(7):1704–1709

    Article  PubMed  CAS  Google Scholar 

  45. Maskarinec G, Pagano IS, Yamashiro G, Issell BF (2003) Influences of ethnicity, treatment, and comorbidity on breast cancer survival in Hawaii. J Clin Epidemiol 56(7):678–685

    Article  PubMed  Google Scholar 

  46. Ademuyiwa FO, Olopade OI (2003) Racial differences in genetic factors associated with breast cancer. Cancer Metastasis Rev 22(1):47–53

    Article  PubMed  CAS  Google Scholar 

  47. Siiteri PK, Simberg N, Murai J (1986) Estrogens and breast cancer. Ann NY Acad Sci 464:100–105

    Article  PubMed  CAS  Google Scholar 

  48. Feigelson HS, Henderson BE (1996) Estrogens and breast cancer. Carcinogenesis 17(11):2279–2284

    Article  PubMed  CAS  Google Scholar 

  49. Zhang Y, Wat N, Stratton IM, Warren-Perry MG, Orho M, Groop L, Turner RC (1996) UKPDS 19: heterogeneity in NIDDM: separate contributions of IRS-1 and b3-adrenergic-receptor mutations to insulin resistance and obesity respectively with no evidence for glycogen synthase gene mutations. Diabetologia 39(12):1505–1511

    Article  PubMed  CAS  Google Scholar 

  50. Ito K, Katsuki A, Furuta M, Fujii M, Tsuchihashi K, Hori Y, Yano Y, Sumida Y, Adachi Y (1999) Insulin sensitivity is not affected by mutation of codon 972 of the human IRS-1 gene. Horm Res 52(5):230–234

    Article  PubMed  CAS  Google Scholar 

  51. Previs SF, Withers DJ, Ren J-M, White MF, Shulman GI (2000) Contrasting effects of IRS-1 versus IRS-2 gene disruption on carbohydrate and lipid metabolism in vivo. J Biol Chem 275(50):38990–38994

    Article  PubMed  CAS  Google Scholar 

  52. Yamauchi T, Tobe K, Tamemoto H, Ueki K, Kaburagi Y, Yamamoto-Honda R, Takahashi Y, Yoshizawa F, Aizawa S, Akanuma Y, et al (1996) Insulin signalling and insulin actions in the muscles and livers of insulin-resistant, insulin receptor substrate 1-deficient mice. Mol Cell Biol 16(6):3074–3084

    PubMed  CAS  Google Scholar 

  53. Porzio O, Federici M, Hribal ML, Lauro D, Accili D, Lauro R, Borboni P, Sesti G (1999) The Gly972->Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic {beta} cells. J Clin Invest 104(3):357–364

    Article  PubMed  CAS  Google Scholar 

  54. Stoll BA (2002) Upper abdominal obesity, insulin resistance and breast cancer risk. Int J Obes Relat Metab Disord 26(6):747–753

    Article  PubMed  CAS  Google Scholar 

  55. Imai Y, Philippe N, Sesti G, Accili D, Taylor SI (1997) Expression of variant forms of insulin receptor substrate-1 identified in patients with noninsulin-dependent diabetes mellitus. J␣Clin Endocrinol Metab 82(12):4201–4207

    Article  PubMed  CAS  Google Scholar 

  56. Carvalho E, Jansson PA, Axelsen M, Eriksson JW, Huang X, Groop L, Rondinone C, Sjostrom L, Smith U (1999) Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM. Faseb J 13(15):2173–2178

    PubMed  CAS  Google Scholar 

  57. Hager J, Zouali H, Velho G, Froguel P (1993) Insulin receptor substrate (IRS-1) gene polymorphisms in French NIDDM families. Lancet 342(8884):1430

    Article  PubMed  CAS  Google Scholar 

  58. Laakso M, Malkki M, Kekalainen P, Kuusisto J, Deeb SS (1994) Insulin receptor substrate-1 variants in non-insulin-dependent diabetes. J Clin Invest 94(3):1141–1146

    Article  PubMed  CAS  Google Scholar 

  59. Chuang LM, Lai CS, Yeh JI, Wu HP, Tai TY, Lin BJ (1996) No association between the Gly971Arg variant of the insulin receptor substrate 1 gene and NIDDM in the Taiwanese population. Diabetes Care 19(5):446–449

    Article  PubMed  CAS  Google Scholar 

  60. Armstrong M, Haldane F, Taylor RW, Humphriss D, Berrish T, Stewart MW, Turnbull DM, Alberti KG, Walker M (1996) Human insulin receptor substrate-1: variant sequences in familial non-insulin-dependent diabetes mellitus. Diabet Med 13(2):133–138

    Article  PubMed  CAS  Google Scholar 

  61. Armstrong M, Haldane F, Avery PJ, Mitcheson J, Stewart MW, Turnbull DM, Walker M (1996) Relationship between insulin sensitivity and insulin receptor substrate-1 mutations in non-diabetic relatives of NIDDM families. Diabet Med 13(4):341–345

    Article  PubMed  CAS  Google Scholar 

  62. Ura S, Araki E, Kishikawa H, Shirotani T, Todaka M, Isami S, Shimoda S, Yoshimura R, Matsuda K, Motoyoshi S, et al (1996) Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese patients with NIDDM: identification of five novel polymorphisms. Diabetologia 39(5):600–608

    Article  PubMed  CAS  Google Scholar 

  63. Koch M, Rett K, Volk A, Maerker E, Haist K, Deninger M, Renn W, Haring HU (1999) Amino acid polymorphism Gly 972 Arg in IRS-1 is not associated to lower clamp-derived insulin sensitivity in young healthy first degree relatives of patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 107(5):318–322

    Article  PubMed  CAS  Google Scholar 

  64. Chang Q, Li Y, White MF, Fletcher JA, Xiao S (2002) Constitutive activation of insulin receptor substrate 1 is a frequent event in human tumors: therapeutic implications. Cancer Res 62(21):6035–6038

    PubMed  CAS  Google Scholar 

  65. Lee AV, Zhang P, Ivanova M, Bonnette S, Oesterreich S, Rosen JM, Grimm S, Hovey RC, Vonderhaar BK, Kahn CR, et al (2003) Developmental and hormonal signals dramatically alter the localization and abundance of insulin receptor substrate proteins in the mammary gland.Endocrinology 144(6):2683–2694

    Article  PubMed  CAS  Google Scholar 

  66. Mauro L, Salerno M, Panno ML, Bellizzi D, Sisci D, Miglietta A, Surmacz E, Ando S (2001) Estradiol increases IRS-1 gene expression and insulin signaling in breast cancer cells. Biochem Biophys Res Commun 288(3):685–689

    Article  PubMed  CAS  Google Scholar 

  67. Dupont J, Le Roith D (2001) Insulin-like growth factor 1 and oestradiol promote cell proliferation of MCF-7 breast cancer cells: new insights into their synergistic effects. Mol Pathol 54(3):149–154

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, under Contract Nos. N01-PC-35139, N01-PC-35139 and NIH/NCI/PC-67010. Initial data collection for the Los Angeles County patients was supported by the National Institute of Child Health and Human Development through contract N01 HD 3–3175.

The collection of California cancer incidence data used in this publication was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The ideas and opinions expressed herein are those of the author, and no endorsement by the State of California, Department of Health Services is intended or should be inferred.

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Authors and Affiliations

  1. Integrated Substance Abuse Programs, Neuropsychiatric Institute, University of California, 1640 S. Sepulveda Boulevard, Suite 200, Los Angeles, CA , 90025, USA

    Jing Fan

  2. Department of Preventive Medicine, University of Southern California, Keck School of Medicine, 1441 Eastlake Avenue, MS/44, Los Angeles, CA, 90033, USA

    Roberta McKean-Cowdin, Leslie Bernstein, Arthur Xuejun Li & Frank Gilliland

  3. Department of Obstetrics/Gynecology, University of Southern California, Keck School of Medicine, 1240 N. Mission Road, WCH 1M2, Los Angeles, CA, 90033, USA

    Frank Z. Stanczyk

  4. Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, 20892, USA

    Rachel Ballard-Barbash

  5. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

    Anne McTiernan

  6. Department of Epidemiology and Clinical Investigation Science, University of Louisville, Louisville, KY, 40202, USA

    Richard Baumgartner

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  1. Jing Fan
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  2. Roberta McKean-Cowdin
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Correspondence to Roberta McKean-Cowdin.

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Fan, J., McKean-Cowdin, R., Bernstein, L. et al. An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors. Breast Cancer Res Treat 99, 323–331 (2006). https://doi.org/10.1007/s10549-006-9211-2

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