title: An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors.
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.
authors.affiliation: Integrated Substance Abuse Programs, Neuropsychiatric Institute, University of California, 1640 S. Sepulveda Boulevard, Suite 200, Los Angeles, CA 90025, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.forename: Roberta
authors.initials: R
authors.lastname: McKean-Cowdin
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: Arthur Xuejun
authors.initials: AX
authors.lastname: Li
authors.forename: Rachel
authors.initials: R
authors.lastname: Ballard-Barbash
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.forename: Richard
authors.initials: R
authors.lastname: Baumgartner
authors.forename: Frank
authors.initials: F
authors.lastname: Gilliland
mesh_terms: D001741:Black or African American / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood* / Q000208:ethnology / Q000235:genetics* / Q000628:therapy; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006147:Guanine; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011379:Prognosis; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D017741:Survivors; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: D012739:Gonadal Steroid Hormones; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D006147:Guanine; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein