An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors
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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.
KeywordsAfrican-American Breast cancer IRS-1 Polymorphism Sex hormones
Coefficient of variation
Health, Eating, Activity, and Lifestyle Study
Hormone replacement therapy
Insulin receptor substrate-1
Insulin-like growth factor 1
Insulin-like growth factor 1 receptor
IGF binding proteins
Sex hormone binding globulin
Amino acid change (glycine to arginine) at codon 972
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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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