Both epidemiologic and laboratory investigations have strongly suggested that estrogen plays an important role in the development and progression of breast cancer. Peptide hormones, insulin-like growth factors (IGFs), have potent mitogenic and anti-apoptotic effects on breast cancer cells and high levels of IGF-I are associated with an increased risk of breast cancer. In vitro and in vivo studies have demonstrated that IGFs interact synergistically with estrogen stimulating breast cancer growth. To examine the interplay between estrogen and IGFs in the etiology of breast cancer, we propose to measure plasma levels of these hormones using pre-treatment blood samples collected from a subset of breast cancer cases and controls, as part of a large population-based case-control study in Shanghai, China. The NIH funded large study (R0lCA64277) has recruited 1500 cases and 1500 healthy controls. Participants in the study have provided blood specimens, urine samples, and detailed questionnaire information regarding their demographic features, menstrual and reproductive history, medical history, family history of cancer, lifestyle features and dietary habit. For the proposed study, we will select 200 cases and 200 matched controls from the large study, 100 pairs for each of pre-and postmenopausal women. The cases and controls will be individually matched on age, day of blood collection, and menopausal status, as well as day of menstrual cycle for premenopausal women. Plasma samples of these 400 women will be measured for estradiol, estrone, estrone sulfate, testosterone, dehydroepiandrosterone sulfate (DHEA-S) IGF-I, IGF-II and IGFBP-3 using immunoassays. Associations of these molecules with breast cancer risk as well as the interaction between steroids and IGFs in association with breast cancer risk will be examined in multivariate analyses using the logistic regression model. Findings of the study will provide insights into the etiology of breast cancer and may have potential implications in breast cancer prevention. We will also be able to further confirm our findings by expanding the study to the whole study population if the results are promising.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA083050-02
Application #
6174306
Study Section
Special Emphasis Panel (ZCA1-GRB-S (M2))
Program Officer
Patel, Appasaheb1 R
Project Start
1999-07-01
Project End
2001-08-31
Budget Start
2000-07-01
Budget End
2001-08-31
Support Year
2
Fiscal Year
2000
Total Cost
$24,195
Indirect Cost
Name
Louisiana State University Hsc Shreveport
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Shreveport
State
LA
Country
United States
Zip Code
71103
Sanderson, Maureen; Shu, Xiao Ou; Yu, Herbert et al. (2004) Insulin-like growth factor-I, soy protein intake, and breast cancer risk. Nutr Cancer 50:8-15
Yu, Herbert; Shu, Xiao-Ou; Shi, Runhua et al. (2003) Plasma sex steroid hormones and breast cancer risk in Chinese women. Int J Cancer 105:92-7
Dai, Qi; Franke, Adrian A; Yu, Herbert et al. (2003) Urinary phytoestrogen excretion and breast cancer risk: evaluating potential effect modifiers endogenous estrogens and anthropometrics. Cancer Epidemiol Biomarkers Prev 12:497-502
Yu, Herbert; Shu, Xiao-Ou; Li, Benjamin D L et al. (2003) Joint effect of insulin-like growth factors and sex steroids on breast cancer risk. Cancer Epidemiol Biomarkers Prev 12:1067-73
Kato, I; Eastham, J; Li, B et al. (2003) Genotype-phenotype analysis for the polymorphic CA repeat in the insulin-like growth factor-I (IGF-I) gene. Eur J Epidemiol 18:203-9
Yu, Herbert; Jin, Fan; Shu, Xiao-Ou et al. (2002) Insulin-like growth factors and breast cancer risk in Chinese women. Cancer Epidemiol Biomarkers Prev 11:705-12
Yu, H; Li, B D; Smith, M et al. (2001) Polymorphic CA repeats in the IGF-I gene and breast cancer. Breast Cancer Res Treat 70:117-22
Yu, H; Rohan, T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92:1472-89