Existing epidemiologic studies suggest a complex relationship between obesity and breast cancer, with obesity generally associated with increased risk among postmenopausal women but reduced risk among premenopausal women. Limited information exists on the obesity-breast cancer association for black women, the group with the highest prevalence of obesity, higher incidence of triple negative (and basal-like) breast cancer), but lower incidence of the luminal subtype. It is possible that inconsistent associations between obesity and breast cancer risk in blacks and whites are explained by their differences in underlying mechanisms through which obesity is related to breast cancer risk. Although these mechanisms are not entirely clear, it is in general believed that obesity acts primarily by inducing insulin signaling and resistance, increased estrogen biosynthesis and inflammation to increase the risk of breast cancer. The relative contribution of these mechanisms to the pathogenesis of breast cancer may differ between blacks and whites, which may contribute to racial difference in risk of breast cancer by subtype. We propose herein a case- control study of postmenopausal breast cancer nested within the prospective Southern Community Cohort Study that is tracking over 50,000 women, two-thirds of whom are black, for breast and other cancer incidence. This cohort was recruited from a low-income population where obesity is common (58% of SCCS black women have a BMI>30 kg/m^.
Specific aims are:
Aim 1. To determine whether circulating levels of IGF1, IGF-binding protein 3, adiponectin, leptin, CRP and sex hormones [estradiol, estrone, testosterone and sex hormone-binding globulin (SHBG)] are associated with risk of postmenopausal breast cancer, and whether they differ by race and/or tumor estrogen/progesterone receptor status.
Aim 2. To determine whether the obese state upregulates tumor IGF1 signaling, estrogen receptor (ER) signaling and inflammation gene expression signatures to increase breast cancer risk, and if the extent of upregulation differs by race Aim 3. To determine whether pre-diagnostic circulating levels of IGF1, sex hormones and inflammation markers are associated with IGF1 signaling, ER signaling and inflammation gene expression signatures, respectively, in breast cancer tissues
The results of this study will enhance our understanding of specific pathways through which obesity increases breast cancer risk, particularly among black women. For the first time, through this SPORE Project, a study will use prospectively derived risk estimates for large numbers of black women. This new information may assist in the development of breast cancer prediction models, perhaps specific to race, and testable biomarkers, thus providing novel targets for development of rational therapies for the prevention of breast cancer.
|Bhola, Neil E; Jansen, Valerie M; Bafna, Sangeeta et al. (2015) Kinome-wide functional screen identifies role of PLK1 in hormone-independent, ER-positive breast cancer. Cancer Res 75:405-14|
|Sanders, Melinda E; Schuyler, Peggy A; Simpson, Jean F et al. (2015) Continued observation of the natural history of low-grade ductal carcinoma in situ reaffirms proclivity for local recurrence even after more than 30 years of follow-up. Mod Pathol 28:662-9|
|Abramson, Vandana G; Lehmann, Brian D; Ballinger, Tarah J et al. (2015) Subtyping of triple-negative breast cancer: implications for therapy. Cancer 121:16-Aug|
|Guo, Yan; Zhao, Shilin; Lehmann, Brian D et al. (2014) Detection of internal exon deletion with exon Del. BMC Bioinformatics 15:332|
|Barnes, Stephanie L; Quarles, C Chad; Yankeelov, Thomas E (2014) Modeling the effect of intra-voxel diffusion of contrast agent on the quantitative analysis of dynamic contrast enhanced magnetic resonance imaging. PLoS One 9:e108726|
|Grieb, Brian C; Chen, Xi; Eischen, Christine M (2014) MTBP is overexpressed in triple-negative breast cancer and contributes to its growth and survival. Mol Cancer Res 12:1216-24|
|Su, Pei-Fang; Li, Chung-I; Shyr, Yu (2014) Sample size determination for paired right-censored data based on the difference of Kaplan-Meier estimates. Comput Stat Data Anal 74:39-51|
|Bi, Xiaohong; Rexer, Brent; Arteaga, Carlos L et al. (2014) Evaluating HER2 amplification status and acquired drug resistance in breast cancer cells using Raman spectroscopy. J Biomed Opt 19:025001|
|Jiang, Junfeng; Jia, Peilin; Shen, Bairong et al. (2014) Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites. Oncotarget 5:6168-77|
|Jiang, Junfeng; Jia, Peilin; Zhao, Zhongming et al. (2014) Key regulators in prostate cancer identified by co-expression module analysis. BMC Genomics 15:1015|
Showing the most recent 10 out of 195 publications