Breast Cancer Research and Treatment

, Volume 99, Issue 3, pp 323–331

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

  • Jing Fan
  • Roberta McKean-Cowdin
  • Leslie Bernstein
  • Frank Z. Stanczyk
  • Arthur Xuejun Li
  • Rachel Ballard-Barbash
  • Anne McTiernan
  • Richard Baumgartner
  • Frank Gilliland
Epidemiology

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.

Keywords

African-American Breast cancer IRS-1 Polymorphism Sex hormones 

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

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Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Jing Fan
    • 1
  • Roberta McKean-Cowdin
    • 2
  • Leslie Bernstein
    • 2
  • Frank Z. Stanczyk
    • 3
  • Arthur Xuejun Li
    • 2
  • Rachel Ballard-Barbash
    • 4
  • Anne McTiernan
    • 5
  • Richard Baumgartner
    • 6
  • Frank Gilliland
    • 2
  1. 1.Integrated Substance Abuse Programs, Neuropsychiatric InstituteUniversity of CaliforniaLos AngelesUSA
  2. 2.Department of Preventive MedicineUniversity of Southern California, Keck School of MedicineLos AngelesUSA
  3. 3.Department of Obstetrics/GynecologyUniversity of Southern California, Keck School of MedicineLos AngelesUSA
  4. 4.Applied Research Program, Division of Cancer Control and Population SciencesNational Cancer InstituteBethesdaUSA
  5. 5.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  6. 6.Department of Epidemiology and Clinical Investigation ScienceUniversity of LouisvilleLouisvilleUSA

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